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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
multi-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:
publication
Title:
Effects of maternal inhalation of carbon black nanoparticles on reproductive and fertility parameters in a four-generation study of male mice
Author:
Skovmand A, Jensen ACO, Maurice C, Marchetti F, Lauvås A, Koponen IK, Jensen KA, Goericke-Pesch S, Vogel U, Hougaard KS
Year:
2019
Bibliographic source:
Particle and Fibre Toxicology 16:13

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Time-mated females were exposed to a mean total suspended particle mass concentration of 4.79 ± 1.86 or 33.87 ± 14.77 mg/m3 for the low and high exposure, respectively. In this study, male fertility parameters were assessed following in utero inhalation exposure to carbon black in four generations of mice.
GLP compliance:
not specified
Remarks:
Study is published in open literature
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Carbon black
EC Number:
215-609-9
EC Name:
Carbon black
Cas Number:
1333-86-4
Molecular formula:
C
IUPAC Name:
Carbon black
Test material form:
solid: nanoform, no surface treatment

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
whole body
Remarks on MMAD:
MMAD not reported
Vehicle:
air
Details on exposure:
One male offspring per litter was used to generate the subsequent generation and assessed for heridatary male reproductive parameters, but two F1 males were bred with a naïve female from some litters.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
The dams were exposed to 4.6 and 37 mg/m3 for 45 min per day
Frequency of treatment:
daily from GD 4 to 18
Doses / concentrationsopen allclose all
Dose / conc.:
4.79 mg/m³ air
Dose / conc.:
33.87 mg/m³ air
Control animals:
yes

Examinations

Sperm parameters (parental animals):
Parameters examined in all male parental generations: testis weight, epididymis weight, daily sperm production, sperm chromatin structure
Postmortem examinations (parental animals):
body and reproductive organ weights
Statistics:
Reproductive parameters were averaged between males from litters originating from the same female in the parental generation
Reproductive indices:
Gestation length, number and loss of implantations
Offspring viability indices:
offspring weight, litter size, sex ratio

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
no effects on testosterone levels
Organ weight findings including organ / body weight ratios:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Effect levels (P0)

open allclose all
Dose descriptor:
NOEC
Effect level:
34 mg/m³ air
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
Key result
Dose descriptor:
NOAEC
Effect level:
> 34 mg/m³ air
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality

Target system / organ toxicity (P0)

Key result
Critical effects observed:
no

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed

Reproductive function / performance (P1)

Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Effect levels (P1)

open allclose all
Dose descriptor:
NOEC
Effect level:
34 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
reproductive function (sperm measures)
Key result
Dose descriptor:
NOAEC
Effect level:
> 34 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
reproductive function (sperm measures)

Target system / organ toxicity (P1)

Key result
Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Clinical biochemistry findings:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed

Effect levels (F1)

open allclose all
Dose descriptor:
NOEC
Generation:
F1
Effect level:
34 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
other: reproductive function
Key result
Dose descriptor:
NOAEC
Generation:
F1
Effect level:
> 34 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
other: reproductive function

Target system / organ toxicity (F1)

Key result
Critical effects observed:
no

Results: F2 generation

General toxicity (F2)

Clinical signs:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed

Effect levels (F2)

Key result
Dose descriptor:
NOAEC
Generation:
F2
Effect level:
> 34 mg/L air (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: sperm parameters

Target system / organ toxicity (F2)

Key result
Critical effects observed:
no

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
In utero exposure to carbon black via maternal whole body inhalation did not affect male-specific reproductive, fertility and litter parameters in four generations of mice.
Executive summary:

Time-mated females were exposed to a mean total suspended particle mass concentration of 4.79 ± 1.86 or 33.87 ± 14.77 mg/m3 for the low and high exposure, respectively. Exposure did not affect gestation and litter parameters in any generation. No significant changes were observed in body and reproductive organ weights, epididymal sperm parameters, daily sperm production, plasma testosterone or fertility.