1,3-dichlorobenzene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and sufficient documented

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Teratogenic potential of inhaled dichlorobenzenes in rats and rabbits

Author:

Hayes WC, Hanley TR, Gushow TS, Johnson KA, John JA

Year:

1985

Bibliographic source:

Fundam Appl Toxicol 5, 190-202 (1985)

Reference 2

Reference Type:

review article or handbook

Title:

1,3-dichlorobenzene - Supplement 2008

Author:

MAK

Year:

2013

Bibliographic source:

The MAK-collection Part I, MAK Value documentation 2013, DFG, Deutsche forschungsgemeinschaft 2013 Wiley-VCH Verlag gmbH & Co. KGaA

Materials and methods

Principles of method if other than guideline:

Ortho-dichlorobenzene (ODCB) and para-dichlorobenzene (PDCB) were evaluated for teratogenic potential in rats (ODCB only) and rabbits. Groups of bred rats and inseminated rabbits were exposed to 0,100,200, or 400 ppm (0.6, 1.2 or 2.4 mg/liter air) of ODCR, groups of inseminated rabbits were exposed to 0, 100, 300, or 800 ppm (0.59, 1.77, and 4.72 mg/liter) of PDCB. Animals were exposed for 6 hr/ day on Days 6 through 15 (rats) or 6 through 18 (rabbits) of gestation.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,2-dichlorobenzene

EC Number:

202-425-9

EC Name:

1,2-dichlorobenzene

Cas Number:

95-50-1

Molecular formula:

C6H4Cl2

IUPAC Name:

1,2-dichlorobenzene

Constituent 2

Reference substance name:

1,4-dichlorobenzene

EC Number:

203-400-5

EC Name:

1,4-dichlorobenzene

Cas Number:

106-46-7

Molecular formula:

C6H4Cl2

IUPAC Name:

1,4-dichlorobenzene

Details on test material:

Ortho-dichlorbenzene was supplied by Standard Chlorine of Delaware, Inc. The test sample was analyzed for chemical purity by gas
chromatography prior to the initiation of the study and was determined to be 98.81% pure.
Para-dichlorobenzene was supplied by The Dow Chemical Company, Midland, Michigan. The test sample was analyzed for chemical purity by gas chromatography prior to the initiation of the study and was determined to be 99.9% pure.

Test animals

Species:

other: rat and rabbit

Strain:

other: Fischer 344 rats and New Zealand White rabbits

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

air

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

Adult virgin female Fisher 344 rats (approximately 175-220 g at breeding) were bred to adult males (one female to one male). The day sperm were found in a vaginal smear was considered Day Zero of gestation. Rabbits (approximately 3.5 to 4.5 kg) were artificially inseminated; the day of artificial insemination was considered Day Zero of gestation.

Duration of treatment / exposure:

Animals were exposed for 6 hr/day on Days 6 through 15 (rats) or Days 6 through 18 (rabbits) of gestation.

Frequency of treatment:

daily

Duration of test:

Test animals were sacrificed by carbon dioxide inhalation on Day 21 of gestation for rats, or Day 29 for rabbits.

No. of animals per sex per dose:

Groups of 30 or 32 bred rats and 28 or 30 inseminated rabbits/dose

Control animals:

yes, concurrent vehicle

Results and discussion

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

1

Dose descriptor:

NOAEC

Remarks:

o-dichlorobenzene (teratogenicity rats)

Effect level:

2.4 mg/L air

Based on:

test mat.

Basis for effect level:

other: teratogenicity

2

Dose descriptor:

NOAEC

Remarks:

o-dichlorobenzene (fetotoxicity rats)

Effect level:

2.4 mg/L air

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Remarks on result:

other: rats - no effects at highest dose

3

Dose descriptor:

NOAEC

Remarks:

o-dichlorobenzene (teratogenicity rabbits)

Effect level:

2.4 mg/L air

Based on:

test mat.

Basis for effect level:

other: teratogenicity

4

Dose descriptor:

NOAEC

Remarks:

o-dichlorobenzene (fetotoxicity rabbits)

Effect level:

2.4 mg/L air

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

5

Dose descriptor:

NOAEC

Remarks:

p-dichlorobenzene (teratogenicity rabbits)

Effect level:

4.72 mg/L air

Based on:

test mat.

Basis for effect level:

other: teratogenicity

6

Dose descriptor:

NOAEC

Remarks:

p-dichlorobenzene (fetotoxicity rabbits)

Effect level:

4.72 mg/L air

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Maternal toxicity, as evidenced by a significant decrease in body weight gain, was observed in all groups of ODCB exposed rats and liver weight was significantly increased in the 400-ppm ODCB-exposed group. Slight maternal toxicity was observed in groups of rabbits exposed to 400 ppm ODCB or 800 ppm PDCB as indicated by significantly decreased body weight gain during the first 3 days of exposure. Inhalation of up to 400 ppm (2.4 mg/l) of ODCB was not teratogenic or fetotoxic in rats, and neither ODCB nor PDCB was teratogenic or fetotoxic in rabbits at exposure levels up to 400 or 800 ppm (2.4 or 4.72 mg/l) , respectively.

Applicant's summary and conclusion

Executive summary:

Ortho-dichlorobenzene (ODCB) and para-dichlorobenzene (PDCB) were evaluated for teratogenic potential in rats (ODCB only) and rabbits. Groups of bred rats and inseminated rabbits were exposed to 0,100,200, or 400 ppm (0.6, 1.2 or 2.4 mg/liter air) of ODCR, groups of inseminated rabbits were exposed to 0, 100, 300, or 800 ppm (0.59, 1.77, and 4.72 mg/liter) of PDCB. Animals were exposed for 6 hr/ day on Days 6 through 15 (rats) or 6 through 18 (rabbits) of gestation.

Maternal toxicity, as evidenced by a significant decrease in body weight gain, was observed in all groups of ODCB exposed rats and liver weight was significantly increased in the 400-ppm ODCB-exposed group. Slight maternal toxicity was observed in groups of rabbits exposed to 400 ppm ODCB or 800 ppm PDCB as indicated by significantly decreased body weight gain during the first 3 days of exposure. Inhalation of up to 400 ppm (2.4 mg/l) of ODCB was not teratogenic or fetotoxic in rats, and neither ODCB nor PDCB was teratogenic or fetotoxic in rabbits at exposure levels up to 400 or 800 ppm (2.4 or 4.72 mg/l) , respectively.

In conclusion, inhalation of ortho- or para-dichlorobenzene vapors was not embryotoxic or teratogenic in rats or rabbits at any of the exposure levels used in this study.