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Effects on fertility

Description of key information

A relevant systemic exposure after oral, dermal or respiratory administration is not expected (see section on toxicokinetics for details). Because a lower bioavailability is expected for the non-nanoforms as compared to the nanoforms and since carbon black, irrespective of form display a similar surface chemistry (the functional groups on surface of their particles are essentially the same but may differ in concentration), differences in toxicological outcome is not expected. Hence the data from the not treated nanoforms are read-across to the non-nanoform (for details on key information, see summaries for nanoforms) 

Link to relevant study records

Referenceopen allclose all

Endpoint:
multi-generation reproductive toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Endpoint-specific read-across justification" attached under section 13.2
Reason / purpose for cross-reference:
read-across source
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
Species:
mouse
Strain:
NMRI
Sex:
male
Analytical verification of doses or concentrations:
yes
Description (incidence and severity):
no effects on testosterone levels
Reproductive function: sperm measures:
no effects observed
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
Key result
Critical effects observed:
no
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)
Key result
Critical effects observed:
no
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
Key result
Critical effects observed:
no
Gross pathological findings:
no effects observed
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
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
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.

Endpoint:
multi-generation reproductive toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
Endpoint-specific read-across justification" attached under section 13.2
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOEL
Effect level:
268 other: µg/animal/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Remarks on result:
other: dosed on gd 7, 10, 15 and 18
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOEC
Effect level:
268 other: µg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: number of offfspring, sex ratio
Key result
Dose descriptor:
NOEC
Generation:
F1
Effect level:
268 other: µg/animal
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: number of offspring and sex ratio
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOEC
Generation:
F2
Effect level:
268 other: µg/animal
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no effects on sex ratio, number of offspring, ESTR mutations
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

A relevant systemic exposure after oral, dermal or respiratory administration is not expected (see section on toxicokinetics for details). Because a lower bioavailability, if any, is expected for the non-nanoforms as compared to the nanoforms and since carbon black, irrespective of form display a similar surface chemistry; the functional groups on surface of their particles are essentially the same but may differ in concentration, differences in toxicological outcome is not expected. Hence the data from the nano forms are read-across to the non nano form (for details on key information, see summaries for nanoforms) 

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Endpoint-specific read-across justification" attached under section 13.2
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Species:
other: rat and mice
Route of administration:
other: oral and inhalation
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: discoloration of faeces was not considered an adverse effect
Key result
Dose descriptor:
LOEC
Effect level:
41.7 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: inflammatory markers in BAL increased; persisted until the end of lactation (weaning) as evidenced in the increase in the number of neutrophils and lymphocytes and DNA damage registered in the livers of dams
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects reported
Key result
Dose descriptor:
NOEC
Effect level:
41.7 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
changes in postnatal survival
other: gestational and deveopmental toxicity
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
The oral No Observed Adverse Effect Level (NOAEL) for maternal toxicity and the No Observed Effect Level (NOEL) for developmental toxicity were both set at 1000 mg/kg bw/day in a study evaluated by the SCCS
Executive summary:

The SCCS summarized the study and reports that the study authors concluded that oral administration of carbon black to pregnant rats at 100, 300 or 1 000 mg/kg bw/d during the sensitive period of organogenesis was well tolerated. There were no adverse maternal changes or any effects on embryo-fetal development. Accordingly, under the conditions of this study, the No Observed Adverse Effect Level (NOAEL) for maternal toxicity and the No Observed Effect Level (NOEL) for developmental toxicity were both set at 1000 mg/kg bw/day. This study is used in a weight of evidence assessment for the developmental toxicity assessment. Together with modelled dataon deposition fractions in the lungs of rats and humans it becomes evidennt that a significant amount of carbon black particles inhaled by rats and humans will be cleared from the lungs into the gastrointestinal tract; making this route of exposure of relevance for the human risk assessment.

In an inhalation study, carbon black was administered to 22 time-mated pregnant C57BL/ 6/BomTac mice at a single concentration of ca. 41.7 mg/m3 from days 8 through 18 of gestation. Twenty-two control animals were exposed concomitantly to air. Traditional gestational and post-gestational parameters were assessed in dams and their offspring. In addition, the investigators sought to answer the question whether inhalation exposure to carbon black caused DNA damage in lung (BAL) and liver cells of exposed dams as well as in the liver of their offspring. Lung inflammation in dams was also monitored. Samples for analysis of DNA damage and lung inflammation were collected 5 and 24 days after cessation of exposure in dams and on post-natal days 2, 22-23 and 50 for DNA analysis in offspring.

Gestational and litter parameters in exposed dams and their offspring were similar to controls. Results for weight gain during gestation and lactation, gestation length, offspring weight at birth, during lactation and maturation, litter size, gender ratio, number of implantations, and post-natal viability were unspectacular when compared to controls.

No effects on DNA strand breaks were noted in BAL fluid cell at any investigation time point. Increased level of DNA damage was observed in the livers of exposed dams at both sampling time points of 5 and 24 days after exposure. In the offspring, the level of DNA strand breaks was higher in liver at weaning and in adolescents, compared to their controls (weaning: 1.4-fold increase, p = 0.001; adolescents: 1.5-fold increase p = 0.011). The level of oxidatively generated DNA damage in the liver of offspring was also determined by the level of formamidopyrimidine DNA glycosylase (FPG) enzyme sensitive sites. There was no consistent increase in oxidatively generated DNA damage in the offspring liver cells at any sampling time point i.e. PND 2 (newborn), PND 22-23 (weaning) or PND 50 (adolescent) (newborn; exposed 0.91 ± 0.27 vs. control 0.71 ± 0.20; weaning exposed 1.05 ± 0.12 vs. control 1.28 ± 0.13; adolescents exposed 0.87 ± 0.10 vs. control 1.20 ± 0.11. All data are presented as lesions per 106base pairs).

BAL analysis indicated the presence of persistent inflammation in the lungs of time-mated mice; evidenced in the increased level of neutrophils in BALfluid compared to their controls 5 and 24 days after exposure (5 days: 11.4-fold increase,p=0.008; 24 days: 11.6-fold increase,p<0.001). Also recorded were mildly increased levels of lymphocytes in BALfluid 5 days after exposure (3.4-fold increase,p=0.020) and total cell counts at both time-points (5 days: 1.5-fold increase,p=0.032; 24 days: 1.2-fold increase,p=0.057).

Endpoint:
developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
(i) Carbon black is of low toxicological activity
No adverse maternal changes or any effects on embryo-foetal development was recorded in an OECD 414 Guideline and GLP study in rats exposed via the oral route (oral) at concentrations 100, 300 or 1000 mg/kg body weight/day during the sensitive period of organogenesis. This study has been assessed by the EU Scientific Committee on Consumer Safety (SCCS 2015). The SCCS concluded that the study is reliable, relevant and adequate for use in the assessment of developmental toxicity of carbon black. Toxicokinetic data as discussed under section 7.1 (toxicokinetics) support the logic of this conclusion. Modelled data on deposition fractions in the lungs of rats and humans show that a significant amount of carbon black particles inhaled by rats and humans will be cleared from the lungs into the gastrointestinal tract; making this route of exposure of relevance for the human risk assessment. Basing their opinion on the findings of this study, the SCCS concluded that oral and dermal exposure to carbon black is of little concern in relation to reproductive toxicity.

Further, in the open literature, one inhalation study was identified in a second species, mouse, in which carbon black was administered at a dose of 42 mg/m3 for 1 hour/day daily from gestation days 8 through 18 to mice (Jackson, Hougaard et al. 2012). This study too reported no gestational or developmental toxicity in the offspring, even under these very high exposure concentrations, which clearly induced persistent lung inflammation as evidenced by inflammatory markers in BAL.

(ii) Toxicokinetic considerations
Toxicokinetic studies on carbon black and similar carbonaceous materials indicate that industrially produced carbon black has a low potential to cross biological barriers and thus will not become systemically available at concentrations that are biologically relevant. Therefore, carbon black is unlikely to reach reproductive organs and tissues and have a direct effect on reproductive functions or the developing organism.

(iii) No significant human exposure
Occupational exposure controls are in place. In consumer products carbon black is tightly bound in a matrix with no release of carbon black nanoparticles
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Species:
rabbit
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Description of key information

No relevant information available.

Mode of Action Analysis / Human Relevance Framework

see set_not treated

Justification for classification or non-classification

The criteria for classification according to the EU CLP Regulation are not met.

Additional information