Carbamodithioic acid, bis(mixed 2-ethylhexyl and 2-methylbutyl and pentyl) derivs., antimony (3+) salts

Long-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not Reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

JUSTIFICATION FOR WEIGHT OF EVIDENCE APPROACH: Analytical techniques sensitive enough to quantify test concentrations at the extremely low levels of solubility and predicted aquatic toxicity of the parent compound and/or possible degradation products are not available for this multi-constituent substance. Similarly, the substance is so highly insoluble in water that any attempt to test it with Daphnia magna could yield results that are confounded by the presence of undissolved test item to which the test organisms would become stuck and immobilized (Aquatic Toxicology, 7 (1985) 145-164). Thus, a weight-of-evidence approach using read-across to a closely related compound and a valid QSAR model is considered sufficient to conclude the substance is expected to be very toxic to aquatic life.

JUSTIFICATION FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH

The source chemical (ferbam) is an acceptable analog to represent the aquatic toxicity of the target chemical (tris[t-ethylhexl and/or 2-methylbutyl and/or pentyl(linear and branched)dithiocarbamoto-S,S']antimony(III)) since both substances are trivalent metal salts of dialkyldithiocarbamates and are expected to cause aquatic toxicity by the same mode of action.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

The source chemical and the target chemical are both trivalent metal salts of dialkyldithiocarbamates, with the former being a mono-constituent substance and the latter being a multi-constituent substance. This difference is not, however, expected to impact the validity of the analog approach.

3. ANALOGUE APPROACH JUSTIFICATION

A mode of action common to all dialkyldithiocarbamates, particularly those that are hydrophobic, is that these molecules are simply a way to bring carbon disulfide or reactive elementary sulphur to the site of action and interfere with metallo-enzymes (Aquatic Toxicology, 7 (1985) 145-164), resulting in inhibition of metabolism at various sites and in various processes. Given this mode of action, neither the iron present in the source chemical nor the antimony present in the target chemical are expected to participate in or differentially impact the aquatic toxicity of any reactive species that might be present.

4. DATA MATRIX

Water solubility and octanol-water partition coefficient (Kow) are of greatest importance with regards to aquatic toxicity of dialkyldithiocarbamates. With regards to these parameters, the two substances do differ, with the source chemical being more water soluble and possessing a lower Kow than the target chemical. Van Leeuwen, et. al. (Aquatic Toxicology, 7 (1985) 145-164) describe a relationship of increasing toxicity with increasing Kow, but excluded substances from their calculations which had Kow's so high and water solubilities so extremely low that the substance could not be tested with Daphnia magna because the neonates stuck to the organic surface layer formed, and died as a consequence, with no mortality otherwise observed. Thus, the toxicity of the source chemical can be considered representative of that portion of the soluble portion of the target chemical or its possible reactive degradation products.

Data source

Reference

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Principles of method if other than guideline:

The experiments were carried out with D. magna in a constant temperature room at 20 + 0.5°C with a 12-h photoperiod. The tests were conducted in 800-ml vessels to which 500-ml test solution was added. The test medium used was 50 micron filtered and UV-sterilized Lake IJssel water, with a pH of 8.1 and a hardness of approximately 225 rag.l-l (as CaCO3). Stock solutions were prepared in this water. In several instances acetone or dimethylsulphoxide were used as solvents for the test compounds. The test solutions were renewed three times a week and were prepared fresh at each renewal. Oxygen concentration and pH were measured at regular intervals. The ratio of concentrations was 1.8; actual concentrations were not verified during the experiments.

The experiments were started with newborn (< 24 h) daphnids from a laboratory stock culture. These were fed daily with 3 x 108 cells.l-1 of the unicellular green alga Chlorella pyrenoidosa. The pooled neonates were randomly distributed into cohorts of ten animals each, in 5-8 toxicant concentrations, a solvent control and a blank control. To allow statistical treatment of the data the experiments were replicated five times. The number of surviving females and the number of neonates produced were recorded daily, the new neonates being removed from the test vessels after counting. At the end of the experiments carapace length of the daphnids was determined from the anterior margin of the head to the base of the caudal spine using an ocular micrometer. When daphnids appeared to be males, these animals were excluded both from fecundity, survival and growth analysis.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ferbam

EC Number:

238-484-2

EC Name:

Ferbam

Cas Number:

14484-64-1

Molecular formula:

C9H18FeN3S6

IUPAC Name:

iron(3+) tris(dimethyldithiocarbamate)

Details on test material:

Supplied by ICN

Specific details on test material used for the study:

Substance Name: Ferric dimethyldithiocarbamate (ferbam)
Purity: >95%

Sampling and analysis

Analytical monitoring:

no

Test solutions

Vehicle:

yes

Remarks:

Acetone or Dimethylsulphoxide

Details on test solutions:

10 animals in 5 to 8 toxicant concentrations, a solvent control and a blank control. To allow statistical treatment of the data the experiments were replicated five times.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

The experiments were started with newborn (< 24 h) daphnids from a laboratory stock culture. These were fed daily with 3 x 108 cells.l-1 of the unicellular green alga Chlorella pyrenoidosa. The pooled neonates were randomly distributed into cohorts of ten animals each, in 5-8 toxicant concentrations.

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Test conditions

Nominal and measured concentrations:

Actual concentrations were not verified during the experiments. 10 animals in 5 to 8 toxicant concentrations, a solvent control and a blank control. To allow statistical treatment of the data the experiments were replicated five times.

Details on test conditions:

The test solutions were renewed three times a week and were prepared fresh at each renewal. Oxygen concentration and pH were measured at regular intervals.

Reference substance (positive control):

no

Results and discussion

Effect concentrations

Key result

Duration:

21 d

Dose descriptor:

LC50

Effect conc.:

0.015 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: 95% C.I. = 13 - 16 mg/L

Details on results:

95% C.I. = 13 - 16 mg/L Growth and reproduction were significantly impacted by survival.

Reported statistics and error estimates:

95% C.I. = 13 - 16 mg/L Growth and reproduction were significantly impacted by survival.

Applicant's summary and conclusion

Validity criteria fulfilled:

not specified

Conclusions:

The chronic aquatic toxicity (21-day LC50) of the read-across substance (ferbam) in Daphnia magna was 0.015 mg/L indicating that the substance is very toxic. Growth and reproduction were significantly impacted by survival.

Executive summary:

In a study conducted equivalent or similar to an OECD 211 Guideline study (GLP status not reported), the chronic aquatic toxicity (21 -day LC50) of the read-across substance (ferbam) in Daphnia magna was 0.015 mg/L indicating that the substance is very toxic. Growth and reproduction were significantly impacted by survival. No NOEC was reported.