Estradiol

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

fish short-term toxicity test on embryo and sac-fry stages

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not specified

Principles of method if other than guideline:

Early life-stage test with exposed fathead minnow covering the period of embryonic and larval development until day 29 post hatch.

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

yes

Test organisms (species):

Pimephales promelas

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

33 d

Remarks on exposure duration:

4 days until hatch and then additionally 29 days post hatching

Duration:

4 d

Dose descriptor:

EC50

Effect conc.:

> 560 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

number hatched

Duration:

29 d

Dose descriptor:

EC50

Effect conc.:

> 560 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

29 d

Dose descriptor:

EC50

Effect conc.:

ca. 270 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

29 d

Dose descriptor:

EC50

Effect conc.:

ca. 300 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Duration:

4 d

Dose descriptor:

EC10

Effect conc.:

ca. 290 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

number hatched

Duration:

29 d

Dose descriptor:

EC10

Effect conc.:

ca. 530 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

29 d

Dose descriptor:

EC10

Effect conc.:

ca. 160 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

29 d

Dose descriptor:

EC10

Effect conc.:

ca. 83 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Hatching EC10 = 290 ng/L ,

larval (28 days post hatch) survival EC10 = 530 ng/L,

larval length increase EC10 = 160 ng/L,

larval weight increase EC10 = 83 ng/L;

Hatching was reduced at the two highest concentrations (170 and 560 ng/l), while survival was reduced at the highest concentration. Length and weight were reduced at the two highest concentration. At test termination several fish were deformed morphologically starting at 170 ng/l.

Validity criteria fulfilled:

yes

Conclusions:

Lowest EC10:: 83 ng/l based on larval weight.

Executive summary:

Starting with 24h old eggs, the embryos, larvae and juvenile fish were exposed continuously to estradiol over 29 days post hatch. Hatching success, mortality and growth was evaluated as prime endpoints.

Results: Hatching EC10 = 290 ng/L , larval (28 days post hatch) survival EC10 = 530 ng/L, larval length increase EC10 = 160 ng/L, larval weight increase 83 ng/L;

Hatching was reduced at the two highest concentrations (170 and 560 ng/l), while survival was reduced at the highest concentration. Length and weight were reduced at the two highest concentrations. At test termination several fish were deformed morphologically starting at 170 ng/l.

Reference 2

Endpoint:

fish life cycle toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 72-5 (Fish Life Cycle Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Partial life-cycle test, where adult fish are exposed over a period of 46 days, and egg laying and hatching of the filial-generation is covered.

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

yes

Test organisms (species):

Pimephales promelas

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

46 d

Duration:

46 d

Dose descriptor:

EC10

Effect conc.:

ca. 26 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

other: eggs/female

Duration:

46 d

Dose descriptor:

EC10

Effect conc.:

ca. 49 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

number of spawns

Duration:

46 d

Dose descriptor:

EC10

Effect conc.:

ca. 28 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

number of eggs/spawn

Duration:

46 d

Dose descriptor:

EC10

Effect conc.:

ca. 84 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

time to hatch

Survival of male fish at the two highest concentration (99 and 180 ng/l) was reduced to 33 -50%.

Reproductive success (eggs/female) was reduced at highest concentration (180 ng/l) and spawn/female from second highest concentration onwards. The most sensitive endpoint was the number off eggs/spawn: EC10 = 26 ng/l.

At termination edema and pale, thin blood was observed at 99 and 180 ng/l. Males developed at 180 ng/l no secondary sexual characteristics.

Vitellogenin induction in adult male fish was observed at higher estradiol concentration.

Validity criteria fulfilled:

yes

Conclusions:

Estradiol influences the fecundity of female fish. The most sensitive endpoint was the number off eggs/spawn: EC10 = 26 ng/l

Executive summary:

Adult fathead minnow were exposed to estradiol over a period of 46 days. Fecundity was the main endpoint studied.

Reproductive success (eggs/female) was reduced at highest concentration (180 ng/l) and spawn/female from second highest concentration. At termination edema and pale, thin blood was observed at 99 and 180 ng/l. Males developed at 180 ng/l no secondary sexual characteristics.

Reference 3

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

no guideline available

Principles of method if other than guideline:

Previously exposed fathead minnow covering the period of embryonic and larval development until day 29 post hatch are used for this test. Animals are exposed up to day 92 post hatch, covering juvenile development until just before maturation.

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

yes

Test organisms (species):

Pimephales promelas

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

63 d

Remarks on exposure duration:

until day 92 post hatch

Duration:

92 d

Dose descriptor:

EC50

Effect conc.:

ca. 570 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

92 d

Dose descriptor:

EC50

Effect conc.:

> 570 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

92 d

Dose descriptor:

EC50

Effect conc.:

>= 24 - <= 2 300 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Duration:

56 d

Dose descriptor:

EC50

Effect conc.:

> 570 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

56 d

Dose descriptor:

EC50

Effect conc.:

>= 270 - <= 440 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

56 d

Dose descriptor:

EC50

Effect conc.:

>= 110 - <= 250 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Duration:

56 d

Dose descriptor:

EC10

Effect conc.:

ca. 200 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

56 d

Dose descriptor:

EC10

Effect conc.:

ca. 59 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

56 d

Dose descriptor:

EC10

Effect conc.:

ca. 8 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Duration:

92 d

Dose descriptor:

EC10

Effect conc.:

ca. 140 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

92 d

Dose descriptor:

EC10

Effect conc.:

ca. 48 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

92 d

Dose descriptor:

EC10

Effect conc.:

ca. 27 ng/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

weight

Survival was reduced at the highest concentration (570 ng/l) for both time points. Length and weight increase was reduced starting at the second highest concentration (160 ng/l) at day 56 and 92. Several fish were deformed morphologically stating at 160 ng/l. Cranial deformities appeared to 86% of the fish at 570 ng/L. Reduction of male or immature fish were found starting at 60 ng/l and higher.

Validity criteria fulfilled:

yes

Conclusions:

Most sensitive effect: Juvenile weight increase (day 56) EC 10 = 8 ng/L

Executive summary:

A chronic study in fathead minnow (Pimephales promelas) was conducted. Starting with 24h old eggs, the embryos, larvae and juvenile fish were exposed continuously to estradiol over 92 days post hatch. Mortality, growth and sexual differentiations was evaluated.

Results:

92 days post hatch: juvenile survival EC10 = 140 ng/L,

juvenile length increase EC10 = 48 ng/L,

juvenile weight increase EC 10 = 27 mg/L,

56 days post hatch: juvenile weight increase was 8 ng/L.

Sexual differentiation was impaire from a concentration of 60 ngL onwards with an increase in morphological females or immature fish.

Description of key information

A chronic study in fathead minnow (Pimephales promelas) was conducted. Starting with 24h old eggs, the embryos, larvae and juvenile fish were exposed continuously to estradiol over 92 days post hatch. Hatching success, mortality, growth and sexual differentiations was evaluated as prime
endpoints.
Additionally, adult fathead minnow were exposed to estradiol over a period of 46 days. Fecundity was the main endpoint studied.
Results: Hatching EC10 = 290 ng/L , larval (28 days post hatch) survival EC10 = 530 ng/L, larval length increase EC10 = 160 ng/L,
larval weight increase 83 ng/L; juvenile (92 days post hatch) survival EC10 = 140 ng/L, juvenile length increase EC10 = 48 ng/L, juvenile weight increase EC 10 = 27 ng/L, juvenile (56 days post hatch) weight increase was 8 ng/L. Sexual differentiation was impaire
from a concentration of 60 ngL onwards with an increase in morphological females or immature fish.
Adult reproduction fecundity EC10 =26 ng/L
In a life-cycle study of medaka reported by Seki et al. (2005), the histologically confirmed sex ratio at 60 days post hatch was significantly changed at E2 concentrations ¿ 28 ng/L. No male fish were observed at E2 concentrations of 92 ng/L. Oocytes in the testes (testis-ova) were occasionally
seen at an E2 concentration of 9 ng/L.
Metcalf et al. (2001) observed a concentration-dependent increase of the incidence and the intensity of testis-ova in medaka at E2 concentrations ¿ 10 ng/L after 100 days exposure.

The effects in fish after long-term exposure with estradiol at concentrations below 0.1 µg/L justify the classification as very toxic to aquatic life with long lasting effects.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

EC10

Effect concentration:

10 ng/L

Additional information

The study was performed according to GLP (report B945).