Registration Dossier

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
January to June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes
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:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
The test animals were mated female Wistar rats. The age at start of test was 13 to 14 weeks.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Details on mating procedure:
Pregnant females were used.
Duration of treatment / exposure:
Pregnant female rats were dosed through daily oral gavage at 0, 100, 300 or 1 000 mg/kg/day (24/group) during the sensitive period of organogenesis [day 5 through day 19 of gestation].
Frequency of treatment:
Daily through days 5 to 19 of gestation.
Duration of test:
Following dosing on gestation days 5 through 19, the dams were killed on gestation day 20 and subjected to macroscopic examination. Usual litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half of the foetuses were also examined for soft tissue anomalies, and remaining foetuses were examined for skeletal anomalies.
Doses / concentrationsopen allclose all
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
24 animals per dose
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

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

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Effect levels (fetuses)

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

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion

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 data on 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.