Mercury

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

no data available

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Results only very briefly described, no details given.

Data source

Reference

Reference Type:

publication

Title:

The distribution of HgCl2 in rat body and its effects on foetus.

Author:

Yang, J.M.; et al.

Year:

1996

Bibliographic source:

Biomed. Environ. Sci. Vol. 9: 437-442 (p. 28)

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Various concentrations of mercury chloride were administered to rats followed by an investigation of the distribution of mercury in organs, testis and placenta. Morphological alterations of examined organs were determined. At the same time, the rates of pregnancy in female animals and fetus mortalitiy, growth and development were observed to determine the effect of the test substance on reproduction.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Mercury chloride

EC Number:

231-430-9

EC Name:

Mercury chloride

Cas Number:

7546-30-7

IUPAC Name:

mercury dichloride

Constituent 2

Reference substance name:

Mercury dichloride

EC Number:

231-299-8

EC Name:

Mercury dichloride

Cas Number:

7487-94-7

IUPAC Name:

mercury dichloride

Details on test material:

- Name of test material (as cited in study report): mercury chloride
- Molecular formula (if other than submission substance): HgCl2
- Physical state: solid
No further details are given.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: rats were supplied by Center of Experimental Animal in Shanghai Medical University
- Weight at study initiation: (P) Males: 130-150 g; Females: 220-250 g
No further details are given

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: no details available

Details on mating procedure:

- M/F ratio per cage: mating was carried out in the ratio of 1:2.
- Proof of pregnancy: sperm in vaginal smear referred to asday 0 of pregnancy.
No further details are reported.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No details are reported.

Duration of treatment / exposure:

The male rats were treated for 12 weeks and the females for 2 weeks.

Frequency of treatment:

daily

Details on study schedule:

no data

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
75 µg/mL mercury chloride
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
7.5 µg/mL mercury chloride
Basis:
nominal in water

No. of animals per sex per dose:

- 30 male and 60 female rats were used.
- 2 treatment groups and 1 control group.

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): rats were divided into 3 groups according to their body weights.

Positive control:

No positive control substance was tested.

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: no details are reported

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): test substance was administerd via drinking water.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

Oestrous cyclicity (parental animals):

no data

Sperm parameters (parental animals):

Parameters examined in P male parental generations: testis weights

Litter observations:

PARAMETERS EXAMINED
- The following parameters were examined in F1 offspring: number of pups, weight and length of the fetuses, the conditions of the dead, and the absorption of fetuses.

GROSS EXAMINATION OF DEAD PUPS: yes, for external and internal abnormalities
- Half of each litter was examined for abnormalities of bone and organs by means of dyeing with alizarine red.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: no data
- Maternal animals: on day 18 of pregnancy, animals were sacrificed.

GROSS NECROPSY: no data

HISTOPATHOLOGY / ORGAN WEIGHTS
- Histopathological examination of ovaries, placenta, testis, liver and kidneys were perfomed after these tissues were fixed in 1% formalin and stained with hematoxylin and eosin.

OTHER
- The concentration of mercury in the blood, placenta, testis, liver and kidneys was detected by CVAAS (cold vapour atomic absorption spectrophotometry).

Postmortem examinations (offspring):

no data

Statistics:

Student's t-test

Reproductive indices:

no data

Offspring viability indices:

no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): no data

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): no data

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS): no data

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): no data

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): no data

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
- The rate of pregnancy in the high dose group was significantly lower than that in the control group, which indicates the existence of a dose-response relationship.
- No differences in the number of corpus luteum in the ovaries indicates that mercury chloride did not affect the formation of corpus luteum in the ovaries.

ORGAN WEIGHTS (PARENTAL ANIMALS): no data

GROSS PATHOLOGY (PARENTAL ANIMALS)
- No observable pathological changes were found in the placenta, ovary, liver or kidneys of the female rats.
- Epithelial cells of the renal proximal convoluted tubule were cloudy and swelling.
- In male rats, the renal corpuscle showed no changes.

HISTOPATHOLOGY (PARENTAL ANIMALS)
- Histopathological examination showed that the seminiferous epithelia were falling off, and sperm release was reduced in the male rats.
- Examination of sperm by electron microscopy showed that particulate fat was increased in sperm cell which suggested degeneration of spermatids.

OTHER FINDINGS (PARENTAL ANIMALS)
- The average amount of inorganic mercury accumulation for each rat in the low and high dose groups were 13.4 mg, 92.4 mg (males) and 2.6 mg, 19.2 mg (females), respectively.
- The concentration of mercury in blood for high and low dose groups was significantly higher than that of the low dose and control groups, respectively.
- Mercury concentrations in the placenta for high and low dose groups were significantly higher than that of the control group, respectively, indicating the presence of obvious barrier against mercury chloride.
- The amount of mercury in the liver and kidneys was significantly higher in the high dose and low dose groups than in low dose and control group showing that the distribution of mercury in the body was mainly in the kidneys and the liver.
- In both male and female rats, the concentration of mercury in the blood correlated positively with mercury concentrations in liver and kidneys.
- In male rats, there were obvious positive correlations between the amount of mercury in blood with that of testes.
- In the testis, the mercury content in two exposure groups were significantly higher than taht in the control group.

Effect levels (P0)

Dose descriptor:

LOEL

Effect level:

7.5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: gross pathology; organ weights; histopathology; litter size; litter weight; pup weight; sperm characterisation

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Details on results (F1)

VIABILITY (OFFSPRING) : not examined

CLINICAL SIGNS (OFFSPRING): not examined

BODY WEIGHT (OFFSPRING)
- Body weight and length of the fetuses in the high, low and control groups were 5.4 g. 5.5 g and 5.6 g and 3.9, 4.1 and 4.2 cm, respectively, showing a decreasing trend with increasing dose, but without statistical significance.

SEXUAL MATURATION (OFFSPRING): not examined

ORGAN WEIGHTS (OFFSPRING): no data

GROSS PATHOLOGY (OFFSPRING)
- Examination of organs and bones of the fetuses showed no abnormalities.

HISTOPATHOLOGY (OFFSPRING): no data

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, effects observed in testes may have affected the rate of pregnancy indication an effect of mercury chloride on male fertility. Based on effects on pregnancy rate and effects in male reproductive organs the low dose level represents a LOEL of 7.5 µg/mL HgCl2 (5.5 µg/mL Hg).

Executive summary:

Male rats were treated for 12 weeks and female rats for 2 prior to mating with either 7.5 or 75 µg/ml HgCl₂ in the drinking water (control group: distilled water). Blood samples taken on day 18 of pregnancy showed that HgCl₂ was absorbed and available in blood as inorganic mercury. The greatest amount of mercury was found in kidneys, and placenta and testes showed also high deposits. Foetuses showed low levels of Hg. There were no differences in the number of corpora lutea among the groups. The number of pregnant female and the corresponding pregnancy rate (8%) was lower in the low dose group (55%) and statistically significantly (p<0.01) decreased in the high dose group (40%) compared to the control (85%). No gross pathological changes were observed in the placenta, liver or kidney of female animals. However, histopathology revealed cloudy and swollen epithelial cells of renal proximal tubules (not observed in males). Histopathological examination of testes showed that seminiferous epithelia were falling off and sperm release was reduced. Electron microscopic examination of sperm showed that particulate fat was increased in sperm cell which suggested degeneration of spermatids.