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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

It is concluded that the substanceTalc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Reproductive toxicity

Link to relevant study records

Referenceopen allclose all

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
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
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
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.
Dose / conc.:
9 mg/kg bw/day
Dose / conc.:
42 mg/kg bw/day
Dose / conc.:
195 mg/kg bw/day
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.
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
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: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
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.
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.
Critical effects observed:
not specified
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
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.
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.
Critical effects observed:
not specified
Reproductive effects observed:
not specified
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.

Endpoint:
two-generation reproductive toxicity
Remarks:
QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction: .Accepted Estrogen Receptor Binding QSAR method for chemicals properties assessment.. This method is relevant for reproductive toxicity endpoints in fish and mammals.
Qualifier:
according to guideline
Guideline:
other: QSAR Toolbox Version 3.3.5.17
Principles of method if other than guideline:
This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.
GLP compliance:
no
Remarks:
not applicable. QSAR model,Estrogen Receptor Binding method, relevant for reproductive toxicity endpoints in fish and mammals.
Limit test:
no
Species:
other: fish (trout) and mammals.
Strain:
other: QSAR model
Sex:
not specified
Route of administration:
other: QSAR model
Vehicle:
other: QSAR model
Details on exposure:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .
Remarks:
Doses / Concentrations:

Basis:
other: QSAR model
Control animals:
not specified
Parental animals: Observations and examinations:
Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .
Clinical signs:
no effects observed
Description (incidence and severity):
QSAR model
Body weight and weight changes:
no effects observed
Description (incidence and severity):
QSAR model
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
QSAR model
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
QSAR model
Other effects:
no effects observed
Description (incidence and severity):
Test substance intake: QSAR model
Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
QSAR model
Reproductive function: sperm measures:
no effects observed
Description (incidence and severity):
QSAR model
Reproductive performance:
no effects observed
Description (incidence and severity):
QSAR model
1.1. CAS number:
7631-86-9
1.2. Other regulatory numbers:
Not reported
1.3. Chemical name(s):
silicon dioxide
silica
silica gel
pyrogenic colloidal silica
dioxosilane
precipitated silica
siliceous earth, purified
silicon dioxide (7631-86-9, 112945-52-5, 112926-00-8)
siliziumdioxid
hochdisperses silizium dioxid (deutsches arzneibuch)
light anhydrous silicic acid (japanese pharmacopoeia)
amorphous synthetic silica gel, crystalline-free
colloidal silicon dioxide (european pharmacopoeia ii)
highly dispersed silica
pyrogenic (fumed) amorphous silica
amorphous, fumed, crystalline-free
silica colloidalis anhydrica
silicium dioxydatum dispersum (Ostreichisches arzneibuch)
silicon dioxide amorphous (who, technical report series)
silicon dioxide (us-food chemicals codex)

1.4. Structure codes:
a. SMILES:
O=[Si]=O
b. Input structure code (if different from SMILES):
Not available
c. Stereochemical features:
Not provided by the user
manually editable field
1.5. Profiling results:
DNA binding by OECD
No alert found
Est rogen Receptor Binding
Non binder, non cyclic structure
OECD HPV Chemical Categories
Amorphous silica silicates
Protein binding by OECD
No alert found
Protein binding potency
Not possible to classify according to these rules (GSH)
Superfragments
No superfragment
Toxic hazard classification by Cramer (original)
High (Class III)
US-EPA New Chemical Categories
Not categorized
QSAR


Dose descriptor:
other: Relative ERBA (Estrogen Receptor Binding Affinity)
Effect level:
< -3 other: Log RBA(Relative Binding Affinities )
Based on:
other: Estrogen receptor (ER) binding
Sex:
not specified
Basis for effect level:
clinical signs
body weight and weight gain
water consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
reproductive performance
other: see 'Remark'
Remarks on result:
other: Generation: QSAR model
Clinical signs:
no effects observed
Description (incidence and severity):
QSAR model
Mortality / viability:
no mortality observed
Description (incidence and severity):
QSAR model
Body weight and weight changes:
no effects observed
Description (incidence and severity):
QSAR model
Sexual maturation:
no effects observed
Description (incidence and severity):
QSAR model
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
QSAR model
Gross pathological findings:
no effects observed
Description (incidence and severity):
QSAR model
Histopathological findings:
no effects observed
Description (incidence and severity):
QSAR model
Talc (Mg3H2(SiO3)4) have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Talc (Mg3H2(SiO3)4) does not cause reproductive toxicity.
1. Category member No.1:
1.1. CAS number:
14807-96-6
1.2. Other regulatory numbers:
Not reported
1.3. Chemical name(s):
Talc
Talc (Mg3H2(SiO3)4)
1.4. Structure codes:
a. SMILES:
O[Si](=O)O{-}.[Mg]{2+}.O{-}[Si](O)=O_O=[Si]1O{-}.[Mg]{2+}.O{-}1_O=[Si]1O{-}.[Mg]{2+}.O{-
}1
1.5. Profiling results:
DNA binding by OECD
No alert found
Estrogen Receptor Binding
Non binder, non cyclic structure
OECD HPV Chemical Categories
Amorphous silica silicates
Protein binding by OECD
No alert found
Protein binding potency
Not possible to classify according to these rules (GSH)
Superfragments
No superfragment
Toxic hazard classification by Cramer (original)
High (Class III)
US-EPA New Chemical Categories
Not categorized
Dose descriptor:
other: Relative ERBA (Estrogen Receptor Binding Affinity)
Generation:
F1
Effect level:
< -3 other: Log RBA(Relative Binding Affinities )
Based on:
other: Estrogen receptor (ER) binding
Sex:
not specified
Basis for effect level:
sexual maturation
clinical signs
mortality
body weight and weight gain
clinical biochemistry
organ weights and organ / body weight ratios
gross pathology
histopathology: neoplastic
other:
Remarks on result:
other: Non-ER binder due to non-cyclic molecular structure.
Reproductive effects observed:
not specified

This grouping method contains simple categories for estrogen receptor (ER) binding. This method is relevant for reproductive toxicity endpoints in fish and mammals.

 

Non-binder, impaired OH or NH2 group

Non-binder without OH or NH2 group

Non-binder, non-cyclic structure

Non-binder, MW > 500

Non-binder, non-cyclic structure– chemicals without cycles and MW =<500

Non-ER binder due to non-cyclic molecular structure.

 

Estrogen receptor (ER) binding is a molecular initiating event much like protein binding that leads to a series of adverse outcomes, which are typically considered reproductive and development hazards. It is an endpoint where several comprehensive databases exist, which has lead to the development of several approaches for using (Q)SARs to predict ER-binding and possible endocrine disruption .

Popular among these are the “four phase” assessment that includes Comparative Molecular Field Analysis (CoMFA) and the Common Reactivity Pattern Approach (COREPA)

Since the RE-binding is a receptor mediated event, particular organic functional groups, size and shape are critical to binding potency.

Talc (Mg3H2(SiO3)4) have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Talc (Mg3H2(SiO3)4) does not cause reproductive toxicity.

Conclusions:
Non-ER binder due to non-cyclic molecular structure.Talc (Mg3H2(SiO3)4) have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Talc (Mg3H2(SiO3)4) does not cause reproductive toxicity.
Executive summary:

Non-ER binder due to non-cyclic molecular structure. Talc (Mg3H2(SiO3)4) have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Talc (Mg3H2(SiO3)4) does not cause reproductive toxicity.

1. Category member No.1:

1.1. CAS number:

14807-96-6

1.2. Other regulatory numbers:

Not reported

1.3. Chemical name(s):

Talc

Talc (Mg3H2(SiO3)4)

1.4. Structure codes:

a. SMILES:

O[Si](=O)O{-}.[Mg]{2+}.O{-}[Si](O)=O_O=[Si]1O{-}.[Mg]{2+}.O{-}1_O=[Si]1O{-}.[Mg]{2+}.O{-

}1

1.5. Profiling results:

DNA binding by OECD

No alert found

Estrogen Receptor Binding

Non binder, non cyclic structure

OECD HPV Chemical Categories

Amorphous silica silicates

Protein binding by OECD

No alert found

Protein binding potency

Not possible to classify according to these rules (GSH)

Superfragments

No superfragment

Toxic hazard classification by Cramer (original)

High (Class III)

US-EPA New Chemical Categories

Not categorized

Endpoint:
fertility, other
Remarks:
Effect of Mg on humoral imune response in rats
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium also should be taken into account
Qualifier:
no guideline followed
Principles of method if other than guideline:
Effect of Mg on humoral imune response in rats which were exposed to various levels of Mg in the diet during their growth, mating, gestation and lactation periods.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprangue-Dawley, Houston Texas
- Weight at study initiation: 35-45 g
- Housing: housed in suspended stainless steel wire-bottom cages
- Diet: ad libitum except during breeding
- Water: ad libitum; deionised water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours dark/light cycle
No further details are given.
Route of administration:
oral: feed
Vehicle:
other: diet
Details on mating procedure:
- During study week 9 and 10, females were mated with stock-diet-fed male Sprague-Dawley rats from 7 p.m. to 7 a.m. for 3 or 4 successive nights.
- Diet was withheld during breeding.
- Pregnancy was determined by the presence of vaginal plugs.
- Prior to parturition, dams were transferred to polycarbone cages.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Magnesium content of all diets was confirmed by atomic absorption spectrophotometry.
Duration of treatment / exposure:
Rats received the diets for 8 week during the postweaning growth period, during mating (2 weeks), gestation and lactation until day 18 or 19 post parturition.
Frequency of treatment:
continously
Details on study schedule:
Age at mating of the mated animals in the study: about 12 weeks
Remarks:
Doses / Concentrations:
49 mmol Mg/kg bw/d
Basis:
nominal in diet
group 1 (adequate)
Remarks:
Doses / Concentrations:
8 mmol Mg/kg bw/d
Basis:
nominal in diet
group 2 (deficient)
Remarks:
Doses / Concentrations:
49 + 41 mmol Mg/kg bw/d
Basis:
nominal in diet
group 3 (adequate, plus supplementation from week 9 onwards)
Remarks:
Doses / Concentrations:
8 + 41 mmol Mg/kg
Basis:
nominal in diet
group 4 (deficient, plus supplementation from week 9 onwards)
No. of animals per sex per dose:
60 female rats were divided into groups of 15 rats each
Control animals:
yes
Details on study design:
Group 1: 49 mmol Mg/kg bw /d
Group 2: 8 mmol Mg kg bw/d
Group 3: 49 mmol Mg/kg bw/d for 8 weeks, supplemented with 41 mmol Mg/kg bw/d from week 9 onwards (total 90 mmol/kg bw/d)
Group 4: 8 mmol Mg/kg bw/d for 8 weeks, supplemented with 41 mmol Mg/kg bw/d from week 9 onwards (total 49 mmol/kg bw/d)

- During the postweaning growth period (8 weeks), groups 1 and 3 received diets which were adequate in magnesium (49 mmol Mg/kg bw/d).
- During the postweaning growth period (8 weeks), groups 2 and 4 were fed restricted-magnesium diets (8 mmol Mg/kg bw/d).
- After the 8-week growth period, groups 3 and 4 received diets which were supplemented with 41 mmol Mg/kg bw/d during mating, gestation and lactation.
Positive control:
no data
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: body weights were recorded weekly during the gestation and lactation and postweaning periods.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: feed intake was recorded weekly during the postweaning period.

WATER CONSUMPTION: No data

OTHER:
Haemolytic plaque assay:
- On day 13 of lactation, dams and randomly selected pups (2/litter) were immunised intraperitoneally, 0.6 mL of 1.3 x 10^9 sheep red blood cells (SRBC) for dams and 0.2 mL of 5 x 10^8 SRBC for pups.
- Pups and dams were killed by exposure to excess ether on day 18 and 19 of lactation, respectively.
- Spleens were removed; placed in tissue culture medium (RPMI 1640) and weighed. The spleens were homogenised, a splenic cell suspension was prepared, added to 0.4% trypan blue and placed on a haemocytometer for the viable cell count. This was the basis for preparation of the lymphocyte suspension for the plaque assay. A solution, prepared from 0.6% agarose, 50% SRBC in saline, lymphocyte suspension, tissue culture medium and guinea pig serum was pipetted onto a petri dish, two aliqots/spleen, two plates/spleen. Plates were incubated at 37°C in a humid atmosphere for a minimum of 2 hours.
- Plaques were counted using a dissecting microscope. Plaque forming cells (PFC) per 10^6 cells and per spleen were determined.
Litter observations:
- Number of pups per litter and pup body weight were recorded at birth and daily during lactation.
Postmortem examinations (parental animals):
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on lactation day 18
- Organs examined: heart, kidney, thymus, liver and one femur were removed, weighed.
- Samples were dried and wet ashed first with nutric acid followed by perchloric acid. Final dilutions were made with 1% lanthanum chloride. Analysis of magnesium and calcium contents of tissues was done by atomic absorption spectrophotometry.
Postmortem examinations (offspring):
not applicable
Statistics:
Data were analysed by one-way analysis of variance and analysis of covariance for weight data using the General Linear Model of the Statistical Analysis System. Mean comparisons were done with the Duncan multiple range test. Level of significance was p<0.05.
Offspring viability indices:
not applicable
Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not examined
Other effects:
not specified
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
- Body weight gain during gestation was highest in group 2 (deficient without supplementation) and lowest in group 1 (adequate without supplementation).
- Weight loss was comparable among groups during lactation; group 2 females lost most body weight.
- Femur and cardiac Mg in group 2 dams was reduced, confirming that Mg deficiency was present.
- Spleen weights and PFC (plaque-forming cells) were not different between groups.
- Thymus weights were reduced in groups 2-4 compared to the group 1 fed adequetly during the entire study.
- Results indicate that maternal magnesium deficiency impaired immunocompetence in offspring, regardless of the presence or absence of pregestational magnesium deficiency
- Magnesium supplementation also was associated with depressed immune function.
Dose descriptor:
NOAEC
Based on:
other: effects of magnesium deficiency and supplementation on humoral immune response in dams and pups
Sex:
female
Basis for effect level:
other: Results indicate that maternal magnesium deficiency impaired immunocompetence in offspring; regardless of the status of pregestational magnesium deficiency, magnesium supplementation did not restore depressed immune function.
Remarks on result:
not determinable
Remarks:
no NOAEC identified
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
> 1 190.95 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 49 mmol/L x 24.305= 1190.95 mg/l 1 kg of water has a volume of 1 L and the mg/kg and mg/L are the same.
Critical effects observed:
not specified
Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not examined
Histopathological findings:
no effects observed
- Litter size at birth was not significantly different between treatment groups and was lowest in the group 1 (adequte).
- Viability of pups varied considerably among groups, but percentage mortality was not significantly different.
- Birth weight was lower in in litters of dams fed magnesium restricted diets (groups 2 and 4).
- Day 17 body weigh was lowest in group 1 (adeqaute).
- Thymic weight of and numbers of plaque-forming cells in pups of group 1 (adeqaute) were higher than in the other groups.
- Spleen weight in pups was lowest in group 2 (deficient without supplementation).
Dose descriptor:
NOAEL
Remarks:
offspring development
Generation:
F1
Effect level:
> 1 190.95 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: 49 mmol/L x 24.305= 1190.95 mg/l 1 kg of water has a volume of 1 L and the mg/kg and mg/L are the same.
Critical effects observed:
not specified
Reproductive effects observed:
not specified
Conclusions:
The results of this study indicate that maternal magnesium deficiency impaired immunocompetence in offspring. Magnesium supplementation of dams during gestation and lactation, regardles of pre-gestational magnesium deficiency state, did not restore immune functions in offspring to control level.
Executive summary:

Weanling rats were maintained on diets which were Mg-adequate (49 mmol Mg/kg), groups 1 and 3, or Mg-deficient (8 mmol Mg/kg), groups 2 and 4, for 8 weeks of growth. During breeding, gestation, and lactation, groups 3 and 4 received diets supplemented with 41 mmol Mg/kg. Femur and cardiac Mg in group 2 dams was reduced, confirming that Mg deficiency was present. Thymic weight from dams and pups and numbers of plaque-forming cells in pups in group 1 were higher than in other groups while splenic weight in pups was lowest in group 2.

Results indicate that maternal magnesium deficiency impaired immunocompetence in offspring.Regardless of the presence or absence ofpregestational magnesium deficiency,magnesium supplementation also was associated with depressed immune function.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
900 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
Oral exposure
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.
The NOAEL was 900 mg/kg bw/day.
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
69.57 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Inhalation exposure:
The oral dose (1600 mg/kg bw/day , Takizawa, T., 2000) for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
1600 mg/kg bw/day
÷1.15m3/kgbw
÷20m3/rat
NOAECrat 69.57 mg/m3

Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
216 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
Dermal exposure:
There are no dermal reproduction studies available.
For dermal exposure we taken that:
-the average weight of rabbits is 2.4kg
-the dose is applied over an area which is approximately 10% of the total body surface=0.24 kg
corrected dermal NOAEL= oral NOAEL
900 mg/kg bw/day x 0.24 kg =
NOAELrat = 216 mg/kg bw/day

Additional information

Non-ER binder due to non-cyclic molecular structure. Talc (Mg3H2(SiO3)4) have a molecular weight of less than 500, but do not possess a cyclic structure is reported to non-binders to the receptor and therefore Talc (Mg3H2(SiO3)4) does not cause reproductive toxicity.

 

Oral exposure

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.

 

The NOAEL was 900 mg/kg bw/day.

   

         

 

Dermal exposure:

 

There are no dermal reproduction studies available.

 

For dermal exposure we taken that:

-the average weight of rabbits is 2.4kg

-the dose is applied over an area which is approximately 10% of the total body surface=0.24 kg

 corrected dermal NOAEL=   oral NOAEL

900 mg/kg bw/day x 0.24 kg =                  

 NOAELrat  = 216 mg/kg bw/day

 

 

 

Inhalation exposure:

The oral dose (1600 mg/kg bw/day , Takizawa, T., 2000) for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             

1600 mg/kg bw/day

÷1.15m3/kgbw

÷20m3/rat

NOAECrat     69.57 mg/m3 

 

 

Effects on developmental toxicity

Description of key information

There are conclusive but not suffcient data for the classification of substanceTalc (Mg3H2(SiO3)4)with regard to Developmental toxicity / teratogenicity

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental 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
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive con-trol in both species.
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
[TEST ANIMALS]
- Groups of 20-24 gravid Wistar rats
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 7 days
[ENVIRONMENTAL CONDITIONS]
- Temperature (°C): 20.8–23.1 °C
- Humidity (%): 38.4–77.8 %
- Air changes (per hr): 10–15 clean, fresh, filtered air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive control.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
not specified
Duration of treatment / exposure:
on days 6-15 of gestation.
Frequency of treatment:
Once a day
Duration of test:
on day 20 of gestation
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
16 mg/kg bw/day
Dose / conc.:
74 mg/kg bw/day
Dose / conc.:
350 mg/kg bw/day
Dose / conc.:
1 600 mg/kg bw/day
No. of animals per sex per dose:
groups of 20-24 gravid Wistar rats
Aspirin was used as a positive control
Control animals:
yes, concurrent vehicle
Details on study design:
Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive con-trol in both species. The mice were killed on day 17 and the rats on day 20 of gestation and the number of implantation sites, resorptions sites, and live and dead fetuses, and the live pup body weights were recorded.
Maternal examinations:
CLINICAL OBSERVATIONS:
- All animals were observed once a day throughout the study on mortality, general condition and gross evidence of clinical signs and symptoms
Detailed physical examinations :
- All animals were once in pretest period, once a week throughout the dosing and recovery periods on central and autonomic nervous system effects, motor activity, and behaviour.
Ovaries and uterine content:
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
Fetal examinations:
- External examinations: Yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Number of abortions:
not examined
Details on maternal toxic effects:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
maternal abnormalities
mortality
other: developmental toxicity
Remarks on result:
other:
Remarks:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Fetal body weight changes:
no effects observed
Details on embryotoxic / teratogenic effects:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
Remarks on result:
other:
Remarks:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
The NOAEL was considered to be 1600 mg/kg bw/day for developmental toxicity study.
The administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Executive summary:

Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive control in both species. The mice were killed on day 17 and the rats on day 20 of gestation and the number of implantation sites, resorptions sites, and live and dead fetuses, and the live pup body weights were recorded. In both mice and rats, the admini-stration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.

Endpoint:
developmental 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
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive control in both species.
GLP compliance:
yes
Limit test:
no
Species:
mouse
Strain:
CD-1
Details on test animals or test system and environmental conditions:
[TEST ANIMALS]
- Groups of 20-22 gravid albino CD-1 mice
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 7 days
[ENVIRONMENTAL CONDITIONS]
- Temperature (°C): 20.8–23.1 °C
- Humidity (%): 38.4–77.8 %
- Air changes (per hr): 10–15 clean, fresh, filtered air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Groups of 20-22 gravid albino CD-1 mice were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive control . The mice were killed on day 17 and the rats on day 20 of gestation and the number of implantation sites, resorptions sites, and live and dead fetuses, and the live pup body weights were recorded.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
not specified
Duration of treatment / exposure:
on days 6-15 of gestation.
Frequency of treatment:
Once a day
Duration of test:
on day 20 of gestation
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
16 mg/kg bw/day
Dose / conc.:
74 mg/kg bw/day
Dose / conc.:
350 mg/kg bw/day
Dose / conc.:
1 600 mg/kg bw/day
No. of animals per sex per dose:
Groups of 20-22 gravid albino CD-1 mice
Aspirin was used as a positive control
Control animals:
yes, concurrent vehicle
Details on study design:
Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive con-trol in both species. The mice were killed on day 17 and the rats on day 20 of gestation and the number of implantation sites, resorptions sites, and live and dead fetuses, and the live pup body weights were recorded.
Maternal examinations:
CLINICAL OBSERVATIONS:
- All animals were observed once a day throughout the study on mortality, general condition and gross evidence of clinical signs and symptoms
Detailed physical examinations :
- All animals were once in pretest period, once a week throughout the dosing and recovery periods on central and autonomic nervous system effects, motor activity, and behaviour.
Ovaries and uterine content:
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
Fetal examinations:
- External examinations: Yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Number of abortions:
not examined
Details on maternal toxic effects:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
maternal abnormalities
mortality
other: developmental toxicity
Remarks on result:
other:
Remarks:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Fetal body weight changes:
no effects observed
Details on embryotoxic / teratogenic effects:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
Remarks on result:
other:
Remarks:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
The NOAEL was considered to be 1600 mg/kg bw/day for developmental toxicity study.
The administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Executive summary:

Groups of 20-22 gravid albino CD-1 mice and groups of 20-24 gravid Wistar rats were dosed by gavage with 0, 16, 74, 350, or 1600 mg/kg bw talc as an anhydrous corn oil suspension on days 6-15 of gestation. Aspirin was used as a positive control in both species. The mice were killed on day 17 and the rats on day 20 of gestation and the number of implantation sites, resorptions sites, and live and dead fetuses, and the live pup body weights were recorded. In both mice and rats, the admini-stration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.

Endpoint:
developmental 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
Qualifier:
no guideline followed
Principles of method if other than guideline:
In hamsters, groups of 20-23 gravid female golden hamsters were dosed by gavage with 0, 12, 56, 260, or 1200 mg/kg bw talc as an anhydrous corn oil suspension on days 6-10 of gestation.
GLP compliance:
yes
Limit test:
no
Species:
hamster
Strain:
other: golden hamsters
Details on test animals or test system and environmental conditions:
[TEST ANIMALS]
- Groups of 20-23 gravid female golden hamsters
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 7 days
[ENVIRONMENTAL CONDITIONS]
- Temperature (°C): 20.8–23.1 °C
- Humidity (%): 38.4–77.8 %
- Air changes (per hr): 10–15 clean, fresh, filtered air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
In hamsters, groups of 20-23 gravid female golden hamsters were dosed by gavage with 0, 12, 56, 260, or 1200 mg/kg bw talc as an anhydrous corn oil suspension on days 6-10 of gestation. The animals were killed on day 14 of gestation and examined as described previously
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
not specified
Duration of treatment / exposure:
on days 6-10 of gestation.
Frequency of treatment:
Once a day
Duration of test:
on day 14 of gestation
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
12 mg/kg bw/day
Dose / conc.:
56 mg/kg bw/day
Dose / conc.:
260 mg/kg bw/day
Dose / conc.:
1 200 mg/kg bw/day
No. of animals per sex per dose:
groups of 20-23 gravid female golden hamsters
Control animals:
yes, concurrent vehicle
Details on study design:
In hamsters, groups of 20-23 gravid female golden hamsters were dosed by gavage with 0, 12, 56, 260, or 1200 mg/kg bw talc as an anhydrous corn oil suspension on days 6-10 of gestation. The animals were killed on day 14 of gestation and examined as described previously.
Maternal examinations:
CLINICAL OBSERVATIONS:
- All animals were observed once a day throughout the study on mortality, general condition and gross evidence of clinical signs and symptoms
Detailed physical examinations :
- All animals were once in pretest period, once a week throughout the dosing and recovery periods on central and autonomic nervous system effects, motor activity, and behaviour.
Ovaries and uterine content:
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
Fetal examinations:
- External examinations: Yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Number of abortions:
not examined
Details on maternal toxic effects:
the administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
>= 1 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
maternal abnormalities
mortality
other: developmental toxicity
Remarks on result:
other:
Remarks:
The administration of up to 1200 mg/kg bw talc in corn oil had no reproductive or developmental effects and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Fetal body weight changes:
no effects observed
Details on embryotoxic / teratogenic effects:
The administration of up to 1200 mg/kg bw talc in corn oil had no reproductive or developmental effects and had no effect on maternal or fetal survival.
Dose descriptor:
NOAEL
Effect level:
1 200 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
Remarks on result:
other:
Remarks:
The administration of up to 1200 mg/kg bw talc in corn oil had no reproductive or developmental effects and had no effect on maternal or fetal survival.
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
The NOAEL was considered to be 1200 mg/kg bw/day for developmental toxicity study.
The administration of up to 1200 mg/kg bw talc in corn oil had no reproductive or developmental effects and had no effect on maternal or fetal survival.
Executive summary:

In hamsters, groups of 20-23 gravid female golden hamsters were dosed by gavage with 0, 12, 56, 260, or 1200 mg/kg bw talc as an anhydrous corn oil suspension on days 6-10 of gestation. The animals were killed on day 14 of gestation and examined as described previously. The administration of up to 1200 mg/kg bw talc in corn oil had no reproductive or developmental effects and had no effect on maternal or fetal survival.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 600 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Oral exposure
The NOAEL was considered to be 1600 mg/kg bw/day for developmental toxicity study.
The administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
69.57 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Inhalation exposure:
There are no Inhalation Developmental studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
1600 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 69.57 mg/m3
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Dermal exposure:
There are no dermal Developmental studies available.
For dermal exposure we taken that:
-the average weight of rats is 0.250 g
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
1600 mg/kg bw/day x 0.025 kg =
NOAELrat = 40 mg/kg bw/day
Additional information

There are conclusive but not suffcient data for the classification of substanceTalc (Mg3H2(SiO3)4)with regard to Developmental toxicity / teratogenicity

 

Oral exposure

 

The NOAEL was considered to be 1600 mg/kg bw/day for developmental toxicity study.

The administration of up to 1600 mg/kg bw talc in corn oil had no effect on reproductive or developmental parameters and had no effect on maternal or fetal survival.

 

The NOAEL was 1600 mg/kg bw/day.

 

Inhalation exposure:

There are no Inhalation Developmental studies available.

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             

 1600 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    69.57 mg/m3

 

 

Dermal exposure:

 

There are no dermal Developmental studies available.

 

For dermal exposure we taken that:

-the average weight of rats is 0.250 g

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

1600 mg/kg bw/day x 0.025 kg =                  

 NOAELrat  = 40 mg/kg bw/day

 

Toxicity to reproduction: other studies

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction: other studies
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Pure talc has the formula Mg3Si4O10(OH)2 and a chemical composition of 31.88% by weight (wt) magnesium oxide (MgO), therefore the health effects of Magnesium oxide also should be taken into account
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not specified
GLP compliance:
not specified
Type of method:
in vivo
Species:
other: hen
Strain:
other: laying
Sex:
female
Route of administration:
oral: feed
Vehicle:
other: corn and soiabean meal
Details on exposure:
To study the effects of supplemental magnesium in diets of laying hens on egg production and egg quality parameters, magnesium oxide (38% Mg) was used
Analytical verification of doses or concentrations:
not specified
Remarks:
Doses / Concentrations:
125 mg/Kg Mg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
250 mg/Kg Mg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
500 mg/Kg Mg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
750 mg/Kg Mg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1000 mg/Kg Mg
Basis:
nominal in diet
No. of animals per sex per dose:
5
Control animals:
yes
Dose descriptor:
dose level: oral feed
Effect level:
>= 1 000 mg/kg diet
Based on:
dissolved
Remarks:
magnesium
Sex:
female
Basis for effect level:
clinical signs
Results showed that layer performance including rate of egg production, egg wt, Haugh units, yolk color, shell break force, feed conversion, and body weight gain, was not influenced by the levels of supplemental Mg used.
Conclusions:
Results showed that layer performance including rate of egg production, egg wt, Haugh units, yolk color, shell break force, feed conversion, and body weight gain, was not influenced by the levels of supplemental Mg used.
Executive summary:

To study the effects of supplemental magnesium in diets of laying hens on egg production and egg quality parameters, magnesium oxide (38% Mg) was used to provide 0, 125, 250, 500, 750 and 1,000 mg/kg supplemental Mg to the rations based upon corn and soybean meal. Each diet was fed to 5 replicates of 5 individually caged hens, following a forced molt. Results showed that layer performance including rate of egg production, egg wt, Haugh units, yolk color, shell break force, feed conversion, and body weight gain, was not influenced by the levels of supplemental Mg used.

Justification for classification or non-classification

Based on the hazard assessment of Talc (Mg3H2(SiO3)4) in section 2.1 and 2.2. in IUCLID6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

 

Directive 67/548

Mutagenicity-Genetic Toxicity

Muta. Cat. 1; R46 May cause heritable genetic damage.

Muta. Cat. 2; R46 May cause heritable genetic damage.

Muta. Cat. 3; R68 Possible risk of irreversible effects.

CLP

Germ cell mutagenicity

Muta. 1A

Muta. 1B

Muta. 2

H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 It is concluded that the substance Talc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

 

Additional information