Talc (Mg3H2(SiO3)4)

Toxicity to reproduction

Administrative data

Endpoint:

two-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Principles of method if other than guideline:

The daily administration of 9, 42, 195, or 900 mg/kg bw talc in corn oil to pregnant rabbits on days 6-18 of gestation

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Talc (Mg3H2(SiO3)4)

EC Number:

238-877-9

EC Name:

Talc (Mg3H2(SiO3)4)

Cas Number:

14807-96-6

Molecular formula:

H2Mg3O12Si4

IUPAC Name:

Talc (Mg3H2(SiO3)4)

Test material form:

solid

Test animals

Species:

rabbit

Strain:

Dutch

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Groups of 12-15 gravid Dutch-belted female rabbits
- Diet: ad libitum, a solid diet
- Water: ad libitum, tap water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26
- Humidity (%): 30-70
- Photoperiod: 12 hours dark/light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Groups of 12-15 gravid Dutch-belted female rabbits were dosed orally with 9, 42, 195, or 900 mg/kg bw talc in corn oil on days 6-18 of gestation. Eight gravid negative controls were given only vehicle and 9 gravid positive controls were dosed with 2.5 mg/kg bw of 6-aminonicotinamide on day 9 of gestation. The dams were killed on day 29 of gestation. A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg bw dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively.

Details on mating procedure:

Groups of 12-15 gravid Dutch-belted female rabbits were used.
No further details are given.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

days 6-18 of gestation

Frequency of treatment:

one time daily

Details on study schedule:

Eight gravid negative controls were given only vehicle and 9 gravid positive controls were dosed with 2.5 mg/kg of 6-aminonicotinamide on day 9 of gestation. The dams were killed on day 29 of gestation. A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

9 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

42 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

195 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

900 mg/kg bw/day

No. of animals per sex per dose:

12-15 gravid Dutch-belted female rabbits

Control animals:

yes

Details on study design:

Groups of 12-15 gravid Dutch-belted female rabbits were dosed orally with 9, 42, 195, or 900 mg/kg bw talc in corn oil on days 6-18 of gestation.
Eight gravid negative controls were given only vehicle and 9 gravid positive controls were dosed with 2.5 mg/kg bw of 6-aminonicotinamide on day 9 of gestation.
The dams were killed on day 29 of gestation. A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg bw dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively.

Examinations

Parental animals: Observations and examinations:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: observed daily before, during, directly and 30 minutes after administration, and once a day during the other periods of the study.

BODY WEIGHT: Yes
- Time schedule for examinations: measured on day 0, 4, 7, 11 and 6-18 of gestation and on day 0, 4, 7, 11, 14, 17 and 21 after parturition.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: measured on day 1, 7, 11, 15, 16 and 18 of gestation and on day 2, 4, 7, 11, 14, 17 and 21 after parturition as one-day consumption beginning from the day before.

OTHER:
- Birth was observed twice daily.
- Nursing and lactation state was checked once daily.
No further details are given.

Oestrous cyclicity (parental animals):

no data

Sperm parameters (parental animals):

no data

Litter observations:

The dams were killed on day 29 of gestation. A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg bw dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively.

Postmortem examinations (parental animals):

Eight gravid negative controls were given only vehicle and 9 gravid positive controls were dosed with 2.5 mg/kg bw of 6-aminonicotinamide on day 9 of gestation.

Postmortem examinations (offspring):

- External examinations: living pups were subjected to external examinations post partum.
- Skeletal examinations: pups not selected for further evaluations were killed (day 4 or day 21) under ether anesthesia and subjected to microscopical observation of skeletal tissues.
- The other F1 pups were anesthetized with ether and killed by exsanguination and subjected to autopsy.

Reproductive indices:

no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not examined

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

Administration of up to 900 mg/kg bw talc on days 6-18 of gestation had no discernible effect on nidation or on maternal or fetal survival.
The number of abnormalities did not differ between test and control animals.

Effect levels (P0)

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

> 900 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

reproductive performance

other: Administration of up to 900 mg/kg bw talc on days 6-18 of gestation had no discernible effect on nidation or on maternal or fetal survival. The number of abnormalities did not differ between test and control animals.

Remarks on result:

other:

Remarks:

Administration of up to 900 mg/kg bw talc on days 6-18 of gestation had no discernible effect on nidation or on maternal or fetal survival. The number of abnormalities did not differ between test and control animals.

Target system / organ toxicity (P0)

Critical effects observed:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Details on results (F1)

The dams were killed on day 29 of gestation.
A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg bw dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively.
Administration of up to 900 mg/kg bw talc on days 6-18 of gestation “had no discernible effect on nidation or on maternal or fetal survival.”
The number of abnormalities did not differ between test and control animals.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 900 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

food consumption and compound intake

other: Administration of up to 900 mg/kg bw talc on days 6-18 of gestation had no discernible effect on nidation or on maternal or fetal survival. The number of abnormalities did not differ between test and control animals.

Target system / organ toxicity (F1)

Critical effects observed:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The daily administration of 900 mg talc/kg body weight to pregnant rabbits on days 6 to 18 of gestation did not show any effect either in the dams or in the foetuse.
No dose-related effects were noted in reproduction function. The NOAEL was considered to be 900 mg/kg bw/day for reproduction toxicity study.

Executive summary:

Groups of 12-15 gravid Dutch-belted female rabbits were dosed orally with 9, 42, 195, or 900 mg/kg bw talc in corn oil on days 6-18 of gestation.Eight gravid negative controls were given only vehicle and 9 gravid positive controls were dosed with 2.5 mg/kg bw of 6-aminonicotinamide on day 9 of gestation. The dams were killed on day 29 of gestation. A total of 1/8, 4/15, 2/12, 5/15, and 2/13 dams of the negative control, 9, 42, 195, and 900 mg/kg bw dose groups, respectively, died or aborted before day 29 of gestation, and the number of live litters for these groups was 6/7, 10/11, 8/10, 10/10, and 7/11, respectively. Administration of up to 900 mg/kg bw talc on days 6-18 of gestation had no discernible effect on nidation or on maternal or fetal survival. The number of abnormalities did not differ between test and control animals.