Carbazole

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Screening test, limited documentation, limited number of toxicological endpoints, low number of dams

Data source

Reference

Reference Type:

publication

Title:

Comparative Developmental Dermal Toxicity and Mutagenicity of Carbazole and Benzo[a]carbazole

Author:

Dutson SM, Booth GM, Schaalje GB, Castle RN, and Seegmiller RE

Year:

1997

Bibliographic source:

Environ Toxicol Chem 16 (10), 2113-2117

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: US EPA (Prenatal developmental toxicity)

Principles of method if other than guideline:

Embryonal/foetal screening during and after intrauterine exposure including perinatal development: Carbazole was dermally administered to pregnant rats from day 0 through day 20 of gestation. Dams were allowed to deliver and all animals including pups were sacrificed at lactation day 4. Dams were examined for signs of toxicity throughout gestation. After sacrifice, uterine content was examined. Pups were weighed after birth and at day 4 of lactation. They were examined externally for gross abnormalities and mortality for each litter was determined on day 1 and 3 of lactation.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carbazole

EC Number:

201-696-0

EC Name:

Carbazole

Cas Number:

86-74-8

Molecular formula:

C12H9N

IUPAC Name:

9H-carbazole

Details on test material:

- Name of test material (as cited in study report): carbazole (purchased from Sigma Chemical, St. Louis, MO, USA)
- No further information on test substance

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wilmington/MA
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 225 - 311 g (females)

ENVIRONMENTAL CONDITIONS
- Temperature_ 64 - 69 °F
- Humidity (%): 40 - 70
- Air changes (per hr): 10 x
- Photoperiod (hrs dark / hrs light):

Administration / exposure

Route of administration:

dermal

Vehicle:

DMSO

Details on exposure:

TEST SITE
- Area of exposure: back of animals

REMOVAL OF TEST SUBSTANCE
- Washing (if done): application site was wiped clean with Webril pads
- Time after start of exposure: 6 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5, 25.0, and 250 mg/kg bw each in 1 mL/kg bw DMSO
- Constant volume used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL/kg bw

USE OF RESTRAINERS FOR PREVENTING INGESTION: yes, Elizabethan collars for 6 h after administration

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: nightly until positive evidence of mating
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: no data
- Proof of pregnancy: vaginal plug or sperm in vaginal smear; referred to as day 0 of pregnanc

Duration of treatment / exposure:

From day 0 through day 20 of gestation

Frequency of treatment:

daily with exposure time of 6 h

Duration of test:

Until lactation day 4 (ca. 26 d)

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 2.5, 25.0, and 250 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

1

Dose descriptor:

NOEL

Effect level:

250 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Dermal irritation (erythema, edema, eschar, and/or dry skin) ranging from slight to moderate was observed at the treatment site of animals in all groups, including the DMSO control group. Severity and frequency were similar in treatment and control group animals. Dermal irritation is not considered to be related with carbazole treatment but to be a result of hygroscopic properties of DMSO.

Applicant's summary and conclusion

Conclusions:

In this dermal developmental toxicity study, carbazole did not induce any maternal or developmental toxic effects up to the highest concentration tested (250 mg/kg bw).