Chromium trioxide

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976 to 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The EU RAR summarises the results of a number of fish chronic studies which, individually, have limitations regarding study design and reliabilty. However the results of these studies when taken as a whole, provide an adequate assessment of chronic toxicity to fish. The data are considered to fulfil the criteria laid down in Annex XI to Regulation 1907/2006: adequate for classification and labelling, adequate coverage of key parameters (reproduction and growth, in addition to other parameters), exposure duration comparable or longer that Article 13(3) methods, adequate documentation provided: EU RAR, of which parts have been copied to this endpoint record. Reliability for endpoint also increased based on test results from several species.

Qualifier:

no guideline followed

Guideline:

other: range of studies

Principles of method if other than guideline:

Several studies reported, collectively, providing a weight-of-evidence to address the endpoint of chronic toxicity.

GLP compliance:

no

Analytical monitoring:

yes

Details on sampling:

Various sampling procedures based on multiple studies

Vehicle:

no

Details on test solutions:

Various media prepared based on multiple studies

Test organisms (species):

other: Range of species used

Test type:

other: Range of test designs used

Water media type:

freshwater

Limit test:

no

Remarks on exposure duration:

Range used from several studies

Post exposure observation period:

None reported

Hardness:

Range used from several studies

Test temperature:

Range used from several studies

pH:

Range used from several studies

Dissolved oxygen:

Range used from several studies

Salinity:

Not applicable

Nominal and measured concentrations:

Range used from several studies

Details on test conditions:

Range used from several studies

Reference substance (positive control):

not specified

Details on results:

Putte et al. (1981b) observed increased sensitivity in younger fish, with LC50 values of 7.6 mg/l at 4 months rising to 45 mg/l at 9 months.
As well as effects on survival, growth and reproduction, chromium (VI) (mainly as potassium dichromate) has been shown to cause a variety of sublethal haemotological, pathological, physiological and behavioural effects. These effects are detailed below.

In experiments with the freshwater fish Channa punctatus, 10 mM and 1.0 mM of chromium (VI) (as potassium dichromate, equivalent to 520 and 52 mg Cr/l) significantly decreased the rate of absorption of xylose (a sugar) by the intestine over 1 hour, whereas 0.01 mM and 0.001 mM (equivalent to 0.52 and 0.052 mg Cr/l) significantly increased the rate of absorption of xylose over the same period (Sastry and Sunita, 1983a).

In another series of experiments with Channa punctatus, fish were exposed to sublethal concentrations of chromium (VI) (as potassium dichromate) of 2.6 mg Cr/l for 15 and 30 days at a pH of 7.4. At the end of the experiment, the fish were dissected and various organs were analysed. At both exposure levels, fish were found to be hyperglycemic and hyperlactemic (elevated blood glucose levels and a decrease in liver glycogen content was seen). An elevation of the activity of enzymes involved in glycolysis and the Kreb’s cycle was also seen in muscles and liver, indicating that the metabolic rate of the exposed fish was higher than that of controls (Sastry and Tyagi, 1982; Sastry and Sunita, 1982 and 1984). Similar results were found in a 120 day exposure to the same concentration (Sastry and Sunita, 1983b).

An experiment was carried out with the freshwater fish Tilapia sparrmanii in order to determine the effect of chromium on blood coagulation at acidic (pH 5), physiological (pH 7.4) and alkaline (pH 9) pHs. Fish were exposed to 0.098 mg/l of potassium dichromate (i.e. 0.034 mg Cr (VI)/l) over 96 hours. Fish exposed to chromium contracted thrombocytopenia (a blood disease caused by a shortage of thrombocytes present in blood) with an increase in water pH (Van Pittius et al., 1992).

Gill and Pant (-1978) found that acute (12 and 24 hours) and chronic exposure (30 and 60 days) of the freshwater fish Barbus conchonius to potassium dichromate (chromium concentration 41.2 mg Cr (VI)/l for acute exposures, 0.687 and 1.03 mg Cr (VI)/l for chronic exposures) in hard water (395 mg/l as CaCO3, pH 7.1), resulted in anomalies in peripheral blood and tissues of fish. Pathological changes were also observed in gills, kidneys and liver of chromium-exposed fish.

A study was carried out to assess the avoidance behaviour of rainbow trout (Oncorhynchus mykiss) pre-exposed to sublethal levels of chromium (VI) (as potassium dichromate). Fish were pre-exposed to chromium (VI) concentrations ranging from 0.01 to 3.0 mg Cr (VI)/l. An avoidance threshold of 0.028 mg Cr (VI)/l was determined for fish not pre-exposed to chromium (VI), while avoidance thresholds for pre-exposed fish increased linearly with the level of preexposure. A level of 0.8 mg Cr (VI)/l was proposed as a critical pre-exposure level for short term recovery of normal chemoreceptive capacity (Anestis and Neufeld, 1986).

Vaile and Calamari (1984) studied the immune response in rainbow trout (Oncorhynchus mykiss) exposed to chromium (VI) (as potassium dichromate) over a 4-month exposure period. Fish were exposed to 0.05 (‘safe’ concentration) and 0.200 (‘effect’ concentration) mg Cr (VI)/l. The kinetics of antibody production against human red blood cells were monitored. Chromium (VI) was ineffective at reducing the humoral immune response, that is, there was no evidence of sublethal effects of the metal on the immune system of fish at the levels tested.

Bogé et al. (1988) investigated effects of chromium (VI) as potassium dichromate on enzymatic activities and transport processes of intestinal brush border membrane (alkaline phosphatase and maltase activities, glycine adsorption) of rainbow trout (Oncorhynchus mykiss). The experiments
were carried out by perfusion for 30 minutes of solutions containing either 141 or 14 mg Cr (VI)/l. The higher concentration was lethal to trout over 24 hours exposure. Chromium (VI) exposure lead to a severe decrease of alkaline phosphatase activity growing more severe with increasing chromium (VI) concentration and with time. An approximate 50% inhibition of activity was observed after 30 min with the 141 mg Cr (VI)/l exposure and after 90 min with 14 mg Cr (VI)/l exposure. Enzyme activity remained low after removal of chromium, indicating no recovery of initial activity. No effect of chromium on maltase activity was observed. Chromium (VI), this time as sodium dichromate, was an inhibitor of glycine absorption in trout at high concentrations: 90% inhibition at 14.1 g Cr (VI)/l whereas concentrations of 1.4 g Cr (VI)/l caused no effect.

Temmink et al. (1983) investigated the mechanism of toxicity of chromium (VI) as sodium chromate in fingerling rainbow trout (Oncorhynchus mykiss). Fingerling trout were exposed to 3.2 mg Cr (VI)/l at pH 6.5 for up to 11 days to induce hyperplasia of the gill epithelium. Hyperplasia disappeared in gills of those fish that survived exposure and recovered in control conditions for 0.5 to 4 weeks. The toxic effect of chromium (VI) was thought to occur by a three step process with the first step being degeneration and eventual death of the epithelial cells - the plasma membrane being the primary target for oxidative action of chromium (VI) (Temmink et al., 1983).

Singh and Sivalingam (1982) investigated the effects of heavy metals, including chromium (VI) (as potassium dichromate), on the activity of the liver enzyme catalase of Sarotherodon mossambicus. High concentrations of chromium (VI) caused inhibition of catalase activity. Catalase activity was inhibited by 21% and 37% at concentrations of 30 mg Cr (VI)/l and 40 mg Cr (VI)/l, respectively.

Brown trout (Salmo trutta, 1 year old), and mirror carp (Cyprinus carpio, 3+ years old) were exposed to low-levels of potassium dichromate, 1.01 mg Cr (VI)/l over 266 days (38 weeks). The humoral antibody response to MS2 bacteriophage was followed using a 50% viral neutralisation assay method. Immuno-suppression was observed in both fish species. Total suppression of the immune response was observed in the carp exposed to chromium (VI) and these fish also showed symptoms of acute toxicosis (moribund within 11 weeks). Other sublethal effects seen in the study included a significant loss in weight in exposed fish compared with controls. (O’Neill, 1981).

Jana and Sahana (1988) reported no change in the levels of free amino acids in muscle or protein in kidney or testis of fish (Clarias batrachus) exposed to sodium chromate (5 mg Cr (VI)/l for 14 days at pH 8.5. A small decrease in the dry weight of certain organs (muscle, liver, kidney, stomach, intestine, testis and ovary) was noted in exposed fish when compared with controls.

Kranz and Gercken (1987) investigated whether sublethal concentrations of potassium dichromate (0.175 and 0.7 mg Cr (VI)/l) induce changes in the occurrence of splenic melano-macrophage centres (MMC) in juvenile plaice (Pleuronectes platessa) after 27 days exposure. Macrophages are cells of the immune system which, amongst others, remove foreign particles and effete or damaged cells from an organism. Chromium accumulated to a level of 0.4 mg/kg at both exposure concentrations. Exposure to both levels of chromium (VI) caused a continuous increase in the frequency of splenic MMC in plaice, although the average size of the MMC decreased, therefore the total area did not increase (Kranz and Gercken, 1987).

The results of the chronic fish toxicity studies evaluated in the EU RAR are summarised below:

Species	Life stage	Endpoint	Value	Reference
Catastomus commersoni	Egg/fry	30-day NOEC (g) 60-day NOEC (g)	0.923a 0.29a	Sauter et al. (1976) Sauter et al. (1976)
Esox lucius	Egg/fry	20-day NOEC (s)	0.538a	Sauter et al. (1976)
Ictalurus punctatus	Egg/fry	30-day NOEC (g) 30-60-day NOEC (g)	0.15a 0.305a	Sauter et al. (1976) Sauter et al. (1976)
Oncorhynchus mykiss	Egg/fry Alevin-juvenile	60-day NOEC (g) 60-day NOEC (s) 8-m NOEC (g) 8-m NOEC (m)	0.051a 0.384a 0.1a 0.2a	Sauter et al. (1976) Sauter et al. (1976) Benoit (1976) Benoit (1976)
Oryzias latipes	Embryo/ larval	40-day NOEC (m) 40-day NOEC (g)	3.5 35	Sloof and Canton (1983) Sloof and Canton (1983)
Pimephales promelas	Larval 4-week egg/larvae larvae	7-day NOEC (g) 7-day NOEC (s) 412-day NOEC (s) 9-w LOEC (g) 412-day NOEC (g) NOEC (r) 60-day NOEC (s) 60-day NOEC (g) 30-day NOEC (g) 30-day NOEC (m)	1.1 4.2 1 0.018* 3.95 >3.95 1 1 0.05a >3.06a	De Graeve et al. (1991) De Graeve et al. (1991) Pickering (1980) Pickering (1980) Pickering (1980) Pickering (1980) Pickering (1980) Pickering (1980) Broderius and Smith Jr. (1979) Broderius and Smith Jr. (1979)
Poecilia reticulata	3-4 week	28-day NOEC (m) 28-day NOEC (g)	3.5 3.5	Sloof and Canton (1983) Sloof and Canton (1983)
Salvelinus fontinalis	Embryo/ juvenile	8-m NOEC (g) 8-m NOEC (m)	0.01a 0.2a	Benoit (1976) Benoit (1976)
Salvelinus namaycush	Egg/fry	60-day NOEC (g) 60-day NOEC (s)	0.105a 0.82a	Sauter et al. (1976) Sauter et al. (1976)

Notes: all results are from tests with potassium dichromate except:

a - sodium dichromate.

All concentrations as Cr. (s) - survival; (m) - mortality; (g) - growth; (r) – reproduction.

* - the authors viewed this result as a temporary effect and did not consider it significant in deriving a maximum allowable concentration. The value has not been included in the derivation of a mean NOEC for growth in the RAR.

Validity criteria fulfilled:

yes

Conclusions:

Based on a review of existing fish data from the EU RAR, an acceptable assessment of chronic toxicity was achieved.

Executive summary:

From the EU RAR the effects of chromium (VI) have been reported on fish of different ages and on survival, growth and reproduction. Chromium (VI) (mainly as potassium dichromate) has been shown to cause a variety of sublethal haemotological, pathological,physiological and behavioural effects on fish.

Reference 2

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

Deviations:

yes

Remarks:

no details on test concentration preparation or assessment of endpoint parameters

GLP compliance:

not specified

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: not specified
- Test concentration separation factor: sqrt(10), approx. 3.2

Test organisms (species):

Oryzias latipes

Details on test organisms:

TEST ORGANISM
- Common name: medaka, Japanese rice fish
- Source: standardized laboratory culture
- Age at study initiation (mean and range, SD): eggs
- Method of breeding: The composition of the standard medium for culturing is presented in section "Any other onformation on materials and methods incl. tables".
- Feeding during test: yes

POST-HATCH FEEDING
- Type/source of feed: Paramecium, Artemia, Micromin
- Amount given: not specified
- Frequency of feeding: not specified

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

40 d

Test temperature:

23 +/- 2°C

Nominal and measured concentrations:

not specified

Details on test conditions:

TEST SYSTEM
- Material, size, headspace, fill volume: 1L test volume per group
- No. of organisms per vessel: 35 fertilized eggs/embryos per vessel

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: The detailed composition of the standard medium for testing is presented in section "Any other information on materials and methods incl. tables".

OTHER TEST CONDITIONS
- Photoperiod: circadic
- Light intensity: not specified

EFFECT PARAMETERS MEASURED (with observation intervals if applicable):
- The effect parameters measured were mortality, growth, behaviour and hatching.

Duration:

40 d

Dose descriptor:

NOEC

Remarks:

hatching growth

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

number hatched

Key result

Duration:

40 d

Dose descriptor:

NOEC

Remarks:

mortality+behaviour

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: mortality+behaviour

Duration:

40 d

Dose descriptor:

NOEC

Remarks:

Mortality

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Reported statistics and error estimates:

The NOEC values are based on the nominal concentrations tested.

Validity criteria fulfilled:

not applicable

Conclusions:

A chronic early life stage toxicity study was conducted with Medaka (Oryzias latipes) exposed to potassium dichromate for a test duration of 40 days under semi-static conditions. The test conditions are well described and comparable to OECD TG 210, thus the results can be considered as reliable for the assessment of the long-term toxicity of the registered substance to fish.
The test was set up with 35 eggs per 1 L test volume for each test vessel of the test groups and the effect parameters measured throughout the test were mortality, growth, behaviour and hatching of the test organisms. Based on the obtained results, a NOEC of nominal 10 mg/L was determined for the parameter mortality and behaviour. The NOEC for the parameters hatching and growth was determined to be nominally 100 mg/L.

Executive summary:

The relative susceptibility of 11 taxonomically different species (bacteria, algae, plants, crustaceans, insects, hydrozoans, molluscs, fish and amphibians) to chemicals was determined by comparing the (semi)chronic toxicity data of 8 test substances, one of them being potassium dichromate. The test was carried out with Medaka (Oryzias latipes) in a way that is comparable to OECD TG 210 for a test duration of 40 days under semi-static conditions including three medium renewals per week. The test was set up with 35 eggs per 1 L test volume for each test vessel of the test groups and the effect parameters measured throughout the test were mortality, growth, behaviour and hatching of the test organisms. Based on the obtained results, a NOEC of nominal 10 mg/L was determined for the parameter mortality and behaviour. The NOEC for the parameters hatching and growth was determined to be nominally 100 mg/L.

Description of key information

 1) Key_ Long-term toxicity to fish by summary of data from European Union Risk Assessment Report: chromium trioxide, sodium chromate, sodium dichromate, ammonium dichromate and potassium dichromate; 3rd. Priority List; Volume 53: NOEC = 0.01 - 35 mg/L (nominal) for several species from various studies with different test durations ranging from 7 to 412 days

2) Key_Long-term toxicity to fish: NOEC (40d) = 10 mg/L (nominal) for the parameters mortality and behaviour of Medaka (Oryzias latipes) exposed to potassium dichromate (semi-static, freshwater, test design comparable to OECD 210)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

NOEC

Effect concentration:

10 mg/L

Additional information

1) From the EU RAR the effects of chromium (VI) have been reported on fish of different ages and on survival, growth and reproduction. Chromium (VI) (mainly as potassium dichromate) has been shown to cause a variety of sublethal haemotological, pathological,physiological and behavioural effects on fish.

2) The relative susceptibility of 11 taxonomically different species (bacteria, algae, plants, crustaceans, insects, hydrozoans, molluscs, fish and amphibians) to chemicals was determined by comparing the (semi)chronic toxicity data of 8 test substances, one of them being potassium dichromate. The test was carried out with Medaka (Oryzias latipes) in a way that is comparable to OECD TG 210 for a test duration of 40 days under semi-static conditions including three medium renewals per week. The test was set up with 35 eggs per 1 L test volume for each test vessel of the test groups and the effect parameters measured throughout the test were mortality, growth, behaviour and hatching of the test organisms. Based on the obtained results, a NOEC of nominal 10 mg/L was determined for the parameter mortality and behaviour. The NOEC for the parameters hatching and growth was determined to be nominally 100 mg/L.