1,4-diisopropylbenzene

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied. Please refer to a full version of Read-across statement attached in the section 13 "Assessment reports".

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The underlying hypothesis for the read-across is that the target and the source substance have similar toxicological properties (including the same target organs) due to their structural similarity, resemblance to their chemical reactivity, and therefore a similar mode of action.
The source substance ‘Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene' is a mixture of structural isomers, 1,3- diisopropylbenzene(target substance) and 1,4-diisopropylbenzene. The physico-chemical properties are highly equivalent based on the high structural similarity. As a conclusion, it is scientifically justified to address the endpoint Short-term toxicity to fish with data on this mixture of isomers.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance: Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene (Diisopropylbenzene), CAS no. 25321-09-9
structural formula: C12H18
Smiles: CC(C)C1=CC=CC=C1C(C)C
Molecular weight: 162 g/mol
CAS 25321-09-9
EC No 246-835-6
purity: not specified

target substance: 1.4-diisopropylbenzene (or p-DIPB)
structural formula: C12H18
Smiles: CC(C)c1ccc(cc1)C(C)C
Molecular weight: 162 g/mol
CAS 100-18-5
EC No 202-826-9
purity: not specified

No additional information is available on purity of the source and the target substances. Both substances are normally of high purity, containing only minor amounts of impurities that do not influence the read-across validity.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

4. DATA MATRIX
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

0.25 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Remarks on result:

other: LC0 referred as NOEC since there was no toxicological symptom observed

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

1.48 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.707 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 0.539-0.935 mg/L

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

0.25 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

* Cases and definitions
Death: No response is observed when stimuli are applied.
Abnormal respiration: Gill movement is different from that of the fish in the control area.
Abnormal swimming: Fish that clearly swim differently from the fish in the control area. Slow, irritable, twitching, spastic, or Inversions, etc.
Inability to swim: The swimmer is moving at the bottom or surface but is unable to swim underwater. Those that are not including overturned and suspended death.

Calculation of results: The mortality rate (%) was calculated from the number of deaths in each concentration zone and the number of specimens (10), and the half lethal concentration (LC50) was calculated by the Binomial, Moving average and Probit methods. The 95 % confidence limits were also calculated.

Water temperature, dissolved oxygen concentration and pH of test solution
The water temperature, dissolved oxygen concentration, and pH of the test solution are shown in Table 6, Table 7, and Table 8, respectively.
The water temperature was 24 ± 1 °C in all test tanks, and the dissolved oxygen concentration was above 60 % of the saturated dissolved oxygen concentration (saturated dissolved oxygen concentration at 2.0 °C: 8.25 mg/L) in all test tanks. pH was within the appropriate range (6.0 to 8.5) for the rearing environment of Japanese medaka.

Cumulative Mortality: None of test organisms were killed during exposure period at solvent control, 0.200 and 0.360 mg/L, however all test organisms were killed at 2.00 mg/L on and after 72 hours. Although at the end of test in the control 1 test fish was killed, the mortality did not exceed 10 %.
Therefore, the test was valid OECD test guideline. The lowest concentration that the test organisms were killed was 0.630 mg/L after 72 hours.

Effect Data (mortality):
LC50 (96hr) = 0.707 mg/L (95% C. I.: 0.539-0.935) (mc)
LC0 (96hr) = 0.250 mg/L (mc)
LC100 (96hr) = 1.48 mg/L (mc)
mc: based on measured concentration

Reported statistics and error estimates:

Data Analysis: Probit method, binomial or Moving average for LC50

Sublethal observations / clinical signs:

Cumulative Mortality:

None of test organisms were killed during exposure period at solvent control, 0.200 and 0.360 mg/L, however, all test organisms were killed at 2.00 mg/L on and after 72 hours. The lowest concentration that the test organisms were killed was 0.630 mg/L after 72 hours. Although at the end of test in the control 1 test fish was killed, the mortality did not exceed 10 %. Therefore the test was valid acc. to OECD test guideline.

Abnormal swimming was observed in the concentration zone above 0.431 mg/L (set value: 0.630 mg/L), and inability to swim was observed in the zone above 0.816 mg/L (set value: 1.10 mg/L). No abnormal symptoms were observed during the exposure period in the control and auxiliary aid control areas.

 

Table. Mortality of the medaka (Oryzias latipes) exposed to the test substance.

Nominal Conc. (mg/L)	Mean Conc. (mg/L)*	Cumulative Number of Dead     (Percent Mortality)
		24 hr.	48 hr.	72 hr.	96 hr.
Control	----	0 (0)	0 (0)	0 (0)	1 (10)
Solvent Control	----	0 (0)	0 (0)	0 (0)	0 (0)
0.200	0.137	0 (0)	0 (0)	0 (0)	0 (0)
0.360	0.250	0 (0)	0 (0)	0 (0)	0 (0)
0.630	0.431	0 (0)	0 (0)	1 (10)	2 (20)
1.100	0.816	0 (0)	2 (20)	2 (20)	5 (50)
2.000	1.48	3 (30)	9 (90)	10 (100)	10 (100)

*geometric mean (mean measured concentration)

 

Toxicity Symptoms

　Observed toxicity symptoms are shown in the Table below.

Abnormal swimming was observed in the concentration zone above 0.431 mg/L (set value: 0.630 mg/L), and inability to swim was observed in the zone above 0.816 mg/L (set value: 1.10 mg/L). No abnormal symptoms were observed during the exposure period in the control and auxiliary aid control areas.

Nominal Conc. (mg/L)	Mean Conc. (mg/L)*	Symptoms     (Symptom - number of fish)
		24 hr.	48 hr.	72 hr.	96 hr.
Control	----	N	N	N	N
Solvent Control	----	N	N	N	N
0.200	0.137	N	N	N	N
0.360	0.250	N	N	N	N
0.630	0.431	AS (2)	AS (5)	AS (5)	AS (8)
1.100	0.816	AS (10)	AS (8)	AS (1); AP (7)	AS (1); AP (4)
2.000	1.48	AS (7)	AP (1)	-	-

a: geometric mean (mean measured concentration)

N: No toxicological symptom was observed (no abnormalities)

-: all fish were dead at this observation time

AS: abnormal swimming

AP: paralyzation

Validity criteria fulfilled:

yes

Remarks:

The mortality rate for the 96-hour exposure was 10 % for the control and 0 % for the control of the aid, indicating that the test was valid.

Conclusions:

The 96 h LC50 = 0.707 mg/L (95 % C.L.: 0.539 - 0.935 mg/L; measured concentrations) was determined.

Executive summary:

An acute toxicity test of the test substance - Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene - on the Japanese medaka (Oryzias latipes was conducted to determine the 96-hour half lethal concentration (LC50). In the study conducted according to OECD Guideline 203 (Fish, Acute Toxicity Test) under GLP compliance, Oryzias latipes were exposed to test item for 96 h. The test was conducted using dispersant, and the estimated values were higher than water solubility, however, analytical monitoring was done. The 96 h LC50 = 0.707 mg/L (95 % C.L.: 0.539 - 0.935 mg/L; measured concentrations) was determined.

Based on the arguments presented in the Read Across statement attached in IUCLID Section 13, it is clear that the source substance, which consists only of the target substance and its structural isomer, shows an identical toxicokinetic pattern. As such, the data presented here could be used to fulfil lthe information requirements for the target substance 1.4-diisopropylbenzene.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied. Please refer to a full version of Read-across statement attached in the section 13 "Assessment reports".

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The underlying hypothesis for the read-across is that the target and the source substance have similar toxicological properties (including the same target organs) due to their structural similarity, resemblance to their chemical reactivity, and therefore a similar mode of action.
The source substance ‘Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene' is a mixture of structural isomers, 1,3- diisopropylbenzene and 1,4-diisopropylbenzene (target substance). The physico-chemical properties are highly equivalent based on the high structural similarity. As a conclusion, it is scientifically justified to address the endpoint Short-term toxicity to fish with data on this mixture of isomers.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance: Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene (Diisopropylbenzene), CAS no. 25321-09-9
structural formula: C12H18
Smiles: CC(C)C1=CC=CC=C1C(C)C
Molecular weight: 162 g/mol
CAS 25321-09-9
EC No 246-835-6
purity: not specified

target substance: 1.4-diisopropylbenzene (or p-DIPB)
structural formula: C12H18
Smiles: CC(C)c1ccc(cc1)C(C)C
Molecular weight: 162 g/mol
CAS 100-18-5
EC No 202-826-9
purity: not specified

No additional information is available on purity of the source and the target substances. Both substances are normally of high purity, containing only minor amounts of impurities that do not influence the read-across validity.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

4. DATA MATRIX
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

Reason / purpose for cross-reference:

read-across source

Analytical monitoring:

yes

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

< 1.36 mg/L

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

0.398 mg/L

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.914 mg/L

95% CI:

>= 0.718 - <= 1.19

Details on results:

- Concentration of the test substance in the test solution
The analysis of the test solution showed that the ratio of the measured value to the set value ranged from 74 to 93 % at the time of preparation of the test solution and from 38 to 65 % after 24 hours. The decrease in concentration was mainly due to volatilization from the water and transfer (uptake and adsorption on the body surface) to the Japanese medaka (Oryzias latipes).

Validity criteria fulfilled:

yes

Conclusions:

Oryzias latipes was exposed to test item for 96 hours. It was determined that LC50 (96h) value is 0.914 mg/L (95 % confidence interval: 0.718-1.19 mg/L)

Executive summary:

The short term toxicity to fish study was performed according to "Test Methods for New Chemical Substances: Algae Growth Inhibition Test, Daphnia Acute Swimming Inhibition Test, and Fish Acute Toxicity Test" Oryzias latipes was exposed to test item - Mixture of 1,3-diisopropylbenzene and 1,4-diisopropylbenzene - for 96 hours. It was determined that LC50 (96h) value is 0.914 mg/L (95 % confidence interval: 0.718-1.19 mg/L).

Based on the arguments presented in the Read Across statement attached in IUCLID Section 13, it is clear that the source substance, which consists only of the target substance and its structural isomer, shows an identical toxicokinetic pattern. As such, the data presented here could be used to fulfil lthe information requirements for the target substance 1.4-diisopropylbenzene.

Reference 3

Endpoint:

short-term toxicity to fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied. Please refer to a full version of Read-across statement attached in the section 13 "Assessment reports".

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The underlying hypothesis for the read-across is that the target and the source substance have similar toxicological properties (including the same target organs) due to their structural similarity, resemblance to their chemical reactivity, and therefore a similar mode of action.
The source substance ‘1,3-diisopropylbenzene' is a structural isomer of 1,4-diisopropylbenzene (target substance). The physico-chemical properties are highly equivalent based on the high structural similarity. As a conclusion, it is scientifically justified to address the endpoint Short-term toxicity to aquatic invertebrates with data on this isomer.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source substance: 1.3-diisopropylbenzene (or m-DIPB)
structural formula: C12H18
Smiles: CC(C)c1cccc(c1)C(C)C
Molecular weight: 162 g/mol
CAS 99-62-7
EC No 202-773-1
purity: not specified

target substance: 1.4-diisopropylbenzene (or p-DIPB)
structural formula: C12H18
Smiles: CC(C)c1ccc(cc1)C(C)C
Molecular weight: 162 g/mol
CAS 100-18-5
EC No 202-826-9
purity: not specified

No additional information is available on purity of the source and the target substances. Both substances are normally of high purity, containing only minor amounts of impurities that do not influence the read-across validity.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

4. DATA MATRIX
Please refer to the full version of the read-across statement attached in the section 13 "Assessment reports".

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 0.91 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

>= 0.91 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

No mortality was observed in the control or test substance exposures over the 96 hour exposure.

Sublethal observations / clinical signs:

Summary of Analytical Measurements

Test Vessel	Measured Concentrations (mg/L)			Mean
	0 hr.	48 hr.	96 hr
Control A	ND	ND	ND	ND
Control B	ND	ND	ND	ND
Test A	0.91	0.92	0.86	0.90
Test B	0.92	0.96	0.87	0.92

ND=None Detected

Validity criteria fulfilled:

yes

Conclusions:

No mortality was observed in the control or test concentrations. The 96 hour LC50 was > 0.91 mg/L and the NOEC was ≥ 0.91 mg/L demonstrating no adverse effects at the limit of water solubility.

Executive summary:

The short term toxicity to fish test was performed similar to OECD guideline 203. The test was conducted using a recirculating elutriation system, using 1. 0 g/20 L diluent water to provide a saturated solution. The flow rate was approximately 100 mL/minute passing through the elutriation column. Analytical verification of the exposure concentrations of the source substance 1.3-diisopropylbenzene was conducted at 0, 48, and 96 hours. The mean measured concentrations were 0.90 and 0.92 mg/L for replicates A and B respectively. No mortality was observed in the control or test concentrations. The 96 hour LC50 was > 0.91 mg/L and the NOEC was ≥ 0.91 mg/L demonstrating no adverse effects at the limit of water solubility.

Based on the arguments presented in the Read Across statement attached in IUCLID Section 13, it is clear that the source and the target substances, which are structural isomers, show an identical toxicokinetic pattern. As such, the data presented here can be used to fulfil lthe information requirements for the target substance 1.4-diisopropylbenzene. 

Description of key information

- MOE, 2000c: Orizias latipes, diisopropylbenzene (mixed isomers), 96 h, semi-static, no mortality at the limit of water solubility, LC50 = 0.707 mg/L, LC0 = 0.25 mg/L

- MOE, 2000b: Orizias latipes, diisopropylbenzene (mixed isomers), 96 h, semi-static, LC50 = 0.914 mg/L (95 % confidence interval: 0.718 - 1.19 mg/L). LC0 = 0.398 mg/L

- Ewell, 1986: Pimephales promelas, m-diisopropylbenzene, 96 h, flow-through, no mortality at the limit of water solubility, LC50 > 0.91 mg/L, NOEC ≥ 0.91 mg/L

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

LC50

Effect concentration:

0.707 mg/L

Additional information

A 96 hour acute study with Oryzias latipes was conducted with the mixed isomers (meta and para) of test item under semi-static conditions. The test solutions were prepared using a solvent carrier with resulting test concentrations that exceeded the water solubility of the substance. The test resulted in a LC50 of 0.707 mg/L (95 % C.L.: 0.539 - 0.935 mg/L; measured concentrations) and a LC0 of 0.25 mg/L based upon mean measured concentrations.

 

A further short term toxicity to fish study (MOE, 2000b) was performed according to "Test Methods for New Chemical Substances: Algae Growth Inhibition Test, Daphnia Acute Swimming Inhibition Test, and Fish Acute Toxicity Test". Oryzias latipes was exposed to test item (mixed isomers: meta- and para-diisopropylbenzene) for 96 hours. It was determined that LC50 (96h) value is 0.914 mg/L (95 % confidence interval: 0.718 - 1.19 mg/L).

 

Another 96 hour acute study was performed similar to OECD guideline 203 (Ewell, 1986) and conducted with the test item 1.3-diisopropylbenzene and fathead minnows (Pimephales promelas). The short-term toxicity study was conducted as part of a simultaneous toxicity study using seven species, one vertebrate and six invertebrates. The test was conducted as a limit test using a recirculating column elution apparatus providing a constant saturated solution. Analytical verification of the exposure concentrations was conducted at 0, 48, and 96 hours. The mean measured concentrations were 0.90 and 0.92 mg/L for replicates A and B respectively. No mortality was observed in this test at at the mean measured concentration of 0.91 mg/L. The 96 hour LC50 was > 0.91 mg/L and the NOEC was ≥ 0.91 mg/L demonstrating no adverse effects at the limit of water solubility. The results of these studies suggest no acute effects to fish at the limit of water solubility.

 

Based on the arguments presented in the Read Across statement attached in IUCLID Section 13, it is clear that the source substance, which either consists of the target substance and its structural isomer or is its structural isomer show identical toxicokinetic patterns. As such, the data presented here could be used to fulfil lthe information requirements for the target substance 1.4-diisopropylbenzene.