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Short-term toxicity to fish

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Endpoint:
short-term toxicity to fish
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
Please refer also to the read-across statement attached in section 13

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The target and the source substances are structurally similar substances that share the common organometallic core structure consisting of a central zinc metal bonded to four alkyldithiophosphate esters (ligands) by coordinate covalent bonds -Zn[(S2P(OR)2]2. Structural variations between the target and the source substances are related only to the alkyl (R) groups of the alkyldithiophosphate ligands. The substances in this category give thus rise to an (identical) common compound Phosphorodithioic acid moiety that can be released by the breakage of ester bonds and dissociation from the Zinc complex to which the organism would be exposed if the target substance was tested in the toxicity studies. Exposure to the parent compounds (non-transformed constituents) and to the counter alkyl alcohols, possibly released by hydrolysis of P-O bonds – non-common compounds – would not influence the prediction of the (eco)toxicological properties because they are considered to have the same biological targets and to cause the same type of effects through a common underlying mechanism due to the same functional groups (zinc cation, phosphorodithioic cation and aliphatic alcohol anionic moieties). The impurities of the target and the source substances are not expected to impact the prediction because they are identical or, if slightly structural different, belong to the same class of compounds with the same functional groups and their percentages are very low.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
The aquatic toxicity of the ZDDP category members is mainly influenced by the molecular weight (depends on the length of alkyl rests) and the water solubility. Numerous studies demonstrate decreasing toxicity with the increased chain length. Since the alkyl rests in the target substance are shorter (isobutyl, isopropyl and pentyl) than that of the source substance CAS 4259-15-8 (ethylhexyl) and the water solubility is higher (40.7 mg/L vs 9.1 mg/L for the target and the source substance, respectively) a higher bioavailability is expected for the target substance when compared to source substance CAS 4259-15-8. Regarding the source substances CAS 68457-79-4 and CAS 84605-29-8, the water solubilities are with 1625 and 2764 mg/L above the one of the target substance. Therefore, these source substances are expected to be more bioavailable than the target substance. Thus, data on CAS 68457-79-4 and CAS 84605-29-8 can serve as worst-case data for the target substance. In general, intrinsic toxicities of substances may be the same, because they have the same functional groups and thus the same mode of action. Therefore, taking into account the similar predicted environmental fate and behaviour, the target substance is considered not to possess significantly higher toxicity potential to aquatic environment then the source substance. Thus, the results of the toxicity studies in fish available for the source substances are considered to be similar if these studies were conducted with the target substance. However, the target substance should be classified as aquatic toxic with long-lasting effects because its alkyl chains lengths are shorter (< C8) and thus aquatic toxicity potential cannot be ruled out.
Duration:
96 h
Dose descriptor:
LL50
Effect conc.:
4.5 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: 3.5 - 5.7 mg/L
Duration:
96 h
Dose descriptor:
NOELR
Effect conc.:
1.8 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Details on results:
- Behavioural abnormalities:
Sublethal effects of exposure were observed at the 5.6 mg/L loading rate WAF and above. These responses were increased pigmentation and moribund fish.

- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values:
No insoluble materials were observed in the test solutions. Microscopic inspection of the WAFs showed no microdispersions or undissolved test material to be present.
Results with reference substance (positive control):
No reference tox. data reported
Reported statistics and error estimates:
An estimate of the LL50 values at 3 and 6 hours was given by inspection of the mortality data. The LL50 values at 24 hour as well as the LL50 values and associated confidence limits at 48, 72 and 96 hours were calculated by the maximum likelihood probit method using the ToxCalc computer software package.

Table1. Cumulative Mortality Data

Nominal Test Concentration mg/L

Cumulative Mortality at Hour (Initial population =10 fish)

 

 3      6     24    48   72   96

% Mortality at 96 hours

0, Control

0

0

0

0

0

0

0

1.0

0

0

0

0

0

0

0

1.8

0

0

0

0

0

0

0

3.2

0

0

0

2

2

2

20

5.6

0

0

2

7

7

7

70

10

0

0

4

10

10

10

100

 

 

Table 2. Statistical Analysis of Mortality Data

Exposure Period (hours)

LL50 (mg/L)

95% Confidence Limits (mg/L)

3

>10

--

6

>10

--

24

10

--

48

4.5

3.5 to 5.7

72

4.5

3.5 to 5.7

96

4.5

3.5 to 5.7

Conclusions:
The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated and resulted in a 96 hour LL50 of 4.5 mg/L and a NOEL of 1.8 mg/L.
Executive summary:

Introduction: A study was performed under GLP to assess the acute toxicity of the test material to rainbow trout (Oncorhynchus mykiss) according to OECD TG 203.

 

Methods: Following preliminary range finding studies, fish were exposed in groups of ten to water accommodated fractions of the test material over a range of nominal loading rates of 1.0, 1.8, 3.2, 5.6, and 10 mg/L for a period of 96 hours at a temperature of 14 °C under semi static test conditions. The number of mortalities and any sublethal effects of exposure in each test and control vessel were determined 3 and 6 hours after the start of exposure and then daily throughout the test until termination after 96 hours.

 

Results: The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated and resulted in a 96 hour LL50 of 4.5 mg/L (95% confidence limits of 3.5 to 5.7 mg/L) and a NOEL of 1.8 mg/L.

Endpoint:
short-term toxicity to fish
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
Please refer also to the read-across statement attached in section 13

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The target and the source substances are structurally similar substances that share the common organometallic core structure consisting of a central zinc metal bonded to four alkyldithiophosphate esters (ligands) by coordinate covalent bonds -Zn[(S2P(OR)2]2. Structural variations between the target and the source substances are related only to the alkyl (R) groups of the alkyldithiophosphate ligands. The substances in this category give thus rise to an (identical) common compound Phosphorodithioic acid moiety that can be released by the breakage of ester bonds and dissociation from the Zinc complex to which the organism would be exposed if the target substance was tested in the toxicity studies. Exposure to the parent compounds (non-transformed constituents) and to the counter alkyl alcohols, possibly released by hydrolysis of P-O bonds – non-common compounds – would not influence the prediction of the (eco)toxicological properties because they are considered to have the same biological targets and to cause the same type of effects through a common underlying mechanism due to the same functional groups (zinc cation, phosphorodithioic cation and aliphatic alcohol anionic moieties). The impurities of the target and the source substances are not expected to impact the prediction because they are identical or, if slightly structural different, belong to the same class of compounds with the same functional groups and their percentages are very low.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
The aquatic toxicity of the ZDDP category members is mainly influenced by the molecular weight (depends on the length of alkyl rests) and the water solubility. Numerous studies demonstrate decreasing toxicity with the increased chain length. Since the alkyl rests in the target substance are shorter (isobutyl, isopropyl and pentyl) than that of the source substance CAS 4259-15-8 (ethylhexyl) and the water solubility is higher (40.7 mg/L vs 9.1 mg/L for the target and the source substance, respectively) a higher bioavailability is expected for the target substance when compared to source substance CAS 4259-15-8. Regarding the source substances CAS 68457-79-4 and CAS 84605-29-8, the water solubilities are with 1625 and 2764 mg/L above the one of the target substance. Therefore, these source substances are expected to be more bioavailable than the target substance. Thus, data on CAS 68457-79-4 and CAS 84605-29-8 can serve as worst-case data for the target substance. In general, intrinsic toxicities of substances may be the same, because they have the same functional groups and thus the same mode of action. Therefore, taking into account the similar predicted environmental fate and behaviour, the target substance is considered not to possess significantly higher toxicity potential to aquatic environment then the source substance. Thus, the results of the toxicity studies in fish available for the source substances are considered to be similar if these studies were conducted with the target substance. However, the target substance should be classified as aquatic toxic with long-lasting effects because its alkyl chains lengths are shorter (< C8) and thus aquatic toxicity potential cannot be ruled out.
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
46 mg/L
Nominal / measured:
nominal
Basis for effect:
mortality
Remarks on result:
other: 33 - 61 mg/L
Duration:
96 h
Dose descriptor:
other: NOEL
Effect conc.:
< 26 mg/L
Nominal / measured:
nominal
Basis for effect:
mortality
Details on results:
- Behavioural abnormalities: The NOEL was reported to be less than 26 mg/L, the lowest concentration tested, and this endpoint is based on observations of physical and behavioral abnormalities including lethargy, loss of equilibrium, and darkened pigmentation.

- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: no insoluble materials were reported in the test solutions
Results with reference substance (positive control):
- Results with reference substance valid? Yes. A reference test with sodium lauryl sulfate was conducted with the test fish and the resulting 96 hour LC50 was 1.3 mg/L with a 95% confidence interval of 0.72 to 2.0 mg/L.
Reported statistics and error estimates:
The concentrations tested and the corresponding mortality data derived from the definitive toxicity test were used to estimate the medial LC50 values and 95% confidence intervals using standard statistical computations and software. The statistical methods available were probit analysis, nonlinear interpolation, and moving average analysis.

Table 1. Cumulative Mortality Data

WSF Test Concentration mg/L

Replicate

Cumulative Mortality (%) at Hour

 

24          48      72      96

1000

R1

R2

100

100

100

100

100

100

100

100

400

R1

R2

100

100

100

100

100

100

100

100

160

R1

R2

50

50

80

90

100

90

100

90

64

R1

R2

30

60

50

70

50

80

60

80

26

R1

R2

0

0

0

40

0

40

0

40

0, Control

R1

R2

0

0

0

0

0

0

0

0

  

Table 2. Statistical Analysis of Mortality Data

Exposure Period (hours)

LC50 (mg/L)

95% Confidence Limits (mg/L)

24

100

76 to 140

48

54

37 to 74

72

48

34 to 64

96

46

33 to 61

Validity criteria fulfilled:
yes
Conclusions:
The acute toxicity of the test material to the saltwater fish Cyprinodon variegatus was investigated and resulted in a 96 hour LC50 of 46 mg/L and a NOEL of less than 26 mg/L.
Executive summary:

Introduction: A study was performed under GLP to assess the acute toxicity of the test material to sheepshead minnow (Cyprinodon variegatus) under static renewal test conditions according to OECD TG 203.

 

Methods: Following preliminary range finding studies, fish were exposed in groups of ten to water soluble fractions of the test material at nominal test concentrations of 0, 26, 64, 160, 400, and 1000 mg/L. The test was conducted under static renewal conditions for 96 hours at a temperature of 22 °C. The number of fish mortalities and any sublethal effects were recorded after 24, 48, 72, and 96 hours. 

 

Results: The acute toxicity of the test material to the saltwater fish Cyprinodon variegatus was investigated and resulted in a 96 hour LC50 of 46 mg/L. A reference toxicity test was conducted with sodium lauryl sulfate resulting in a 96 hour LC50 of 1.3 mg/L.

Endpoint:
short-term toxicity to fish
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
Please refer also to the read-across statement attached in section 13

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The target and the source substances are structurally similar substances that share the common organometallic core structure consisting of a central zinc metal bonded to four alkyldithiophosphate esters (ligands) by coordinate covalent bonds -Zn[(S2P(OR)2]2. Structural variations between the target and the source substances are related only to the alkyl (R) groups of the alkyldithiophosphate ligands. The substances in this category give thus rise to an (identical) common compound Phosphorodithioic acid moiety that can be released by the breakage of ester bonds and dissociation from the Zinc complex to which the organism would be exposed if the target substance was tested in the toxicity studies. Exposure to the parent compounds (non-transformed constituents) and to the counter alkyl alcohols, possibly released by hydrolysis of P-O bonds – non-common compounds – would not influence the prediction of the (eco)toxicological properties because they are considered to have the same biological targets and to cause the same type of effects through a common underlying mechanism due to the same functional groups (zinc cation, phosphorodithioic cation and aliphatic alcohol anionic moieties). The impurities of the target and the source substances are not expected to impact the prediction because they are identical or, if slightly structural different, belong to the same class of compounds with the same functional groups and their percentages are very low.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
The aquatic toxicity of the ZDDP category members is mainly influenced by the molecular weight (depends on the length of alkyl rests) and the water solubility. Numerous studies demonstrate decreasing toxicity with the increased chain length. Since the alkyl rests in the target substance are shorter (isobutyl, isopropyl and pentyl) than that of the source substance CAS 4259-15-8 (ethylhexyl) and the water solubility is higher (40.7 mg/L vs 9.1 mg/L for the target and the source substance, respectively) a higher bioavailability is expected for the target substance when compared to source substance CAS 4259-15-8. Regarding the source substances CAS 68457-79-4 and CAS 84605-29-8, the water solubilities are with 1625 and 2764 mg/L above the one of the target substance. Therefore, these source substances are expected to be more bioavailable than the target substance. Thus, data on CAS 68457-79-4 and CAS 84605-29-8 can serve as worst-case data for the target substance. In general, intrinsic toxicities of substances may be the same, because they have the same functional groups and thus the same mode of action. Therefore, taking into account the similar predicted environmental fate and behaviour, the target substance is considered not to possess significantly higher toxicity potential to aquatic environment then the source substance. Thus, the results of the toxicity studies in fish available for the source substances are considered to be similar if these studies were conducted with the target substance. However, the target substance should be classified as aquatic toxic with long-lasting effects because its alkyl chains lengths are shorter (< C8) and thus aquatic toxicity potential cannot be ruled out.
Duration:
96 h
Dose descriptor:
LL50
Effect conc.:
4.4 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: 4.4 - 4.6 mg/L
Duration:
96 h
Dose descriptor:
NOELR
Effect conc.:
3.2 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality
Details on results:
Behavioural abnormalities: Loss of equilibrium in the 5.6 mg/L test group at 48 hours.
- Mortality of control: 0/10
Validity criteria fulfilled:
yes
Conclusions:
The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated and resulted in a 96 hour LL50 of 4.4 mg/L and a NOEL of 3.2 mg/L.
Executive summary:

Introduction: A study was performed under GLP to assess the acute toxicity of the test material to rainbow trout (Oncorhynchus mykiss) according to OECD TG 203.

 

Methods: Fish were exposed in groups of ten to water accommodated fractions of the test material over a range of nominal loading rates of 1.0, 1.8, 3.2, 5.6, and 10 mg/L for a period of 96 hours at a temperature of 14 °C under semi static test conditions. The number of mortalities and any sublethal effects of exposure in each test and control vessel were determined 3 and 6 hours after the start of exposure and then daily throughout the test until termination after 96 hours.

 

Results: The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated and resulted in a 96 hour LL50 of 4.4 mg/L (95% confidence limits of 4.4 to 4.6 mg/L) and a NOEL of 3.2 mg/L.

Description of key information

Source substance Phosphorodithioic acid, mixed O,O-bis(1,3 -dimethylbutyl and iso-Pr) esters, zinc salts (CAS 84605 -29 -8):

The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated under GLP according to OECD guideline 203 in a Klimisch-2 study and resulted in a 96 hour LL50 of 4.5 mg/L (95% confidence limits of 3.5 to 5.7 mg/L) and a NOEL of 1.8 mg/L.

Source substance Zinc bis(O,O-diisobutyl dithiophosphate) (CAS 68457 -79 -4):

The acute toxicity of the test material to the saltwater fish Cyprinodon variegatus was investigated under GLP according to OECD guideline 203 in a Klimisch-2 study and resulted in a 96 hour LC50 of 46 mg/L. A reference toxicity test was conducted with sodium lauryl sulfate resulting in a 96 hour LC50 of 1.3 mg/L.

Source substance Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259 -15 -8):

The acute toxicity of the test material to the freshwater fish Oncorhynchus mykiss was investigated under GLP according to OECD guideline 203 in a Klimisch-2 study and resulted in a 96 hour LL50 of 4.4 mg/L (95% confidence limits of 4.4 to 4.6 mg/L) and a NOEL of 3.2 mg/L

The LL50 -values for the acute toxicity to freshwater fish are slightly differing (4.5 & 4.4 mg/L), but this is in range with the category approach, where nevertheless the members of one category may have different values.

For CSA the lower value is choosen as worst-case-approach .

Key value for chemical safety assessment

LC50 for freshwater fish:
4.4 mg/L
LC50 for marine water fish:
46 mg/L

Additional information

The key value for the CSA for freshwater fish is stated as LL50, not as LC50!