1,2-dichlorobenzene

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Remarks:

repeated dose toxicity studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Histopathology of reproductive organs in repeated dose toxicity studies

Data source

Reference

Reference Type:

publication

Title:

Toxicology and carcinogenesis studies of 1,2-dichlorobenzene (o-dichlorobenzene) (CAS no. 95-50-1) in F344/N rats and B6C3F1 mice (gavage studies)

Author:

National Toxicology Program (NTP)

Year:

1985

Bibliographic source:

Techn. Rep. No. 255, US Dept. of Health and Human Services, Research Triangle Park, N.C. 27709, USA, 1985

Materials and methods

Principles of method if other than guideline:

Several repeated dose toxicity studies were conducted which cover the evaluation of potential toxic effects on the reproductive organs. The National Toxicology Program (1985) administered 1,2-dichlorobenzene by gavage for 13 weeks (0, 30, 60, 125, 250 or 500 mg/kg bw) and two years (0, 60 or 120 mg/kg bw) in male and female rats (F344) and mice (B6C3F1). All studies included the macroscopical and histopathological examination of prostate/testes or ovaries/uterus for all animals or control and high dose group respectively.

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

Details on test material:

- Name of test material (as cited in study report): 1,2-dichlorobenzene
- Analytical purity: >99%
- Impurities (identity and concentrations): 10.8 ppm acidic components (assumed to be hydrochloric acid); GC system: seven further impurities totalling less than 0.07%; two other GC-MS system: 0.7-0.84% 1,4-dichlorobenzene
- Lot/batch No.: SC61377 (ICC Solvent Chemical Company, New York, NY)
- Stability under test conditions: no notable change in the test material; storage conditions were satisfactory over the course of the study
- Storage condition of test material: 22°C in the dark

Test animals

Species:

other: rats and mice

Strain:

other: rats (F344) and mice (B6C3F1)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

13 weeks to 2 years

Frequency of treatment:

daily

Details on study schedule:

Several repeated dose toxicity studies were conducted which cover the evaluation of potential toxic effects on the reproductive organs. The National Toxicology Program (1985) administered 1,2-dichlorobenzene by gavage for 13 weeks (0, 30, 60, 125, 250 or 500 mg/kg bw) and two years (0, 60 or 120 mg/kg bw) in male and female rats (F344) and mice (B6C3F1). All studies included the macroscopical and histopathological examination of prostate/testes or ovaries/uterus for all animals or control and high dose group respectively.

No. of animals per sex per dose:

see chapter repeated dose toxicity

Control animals:

yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Remarks:

reproductive organs

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: None of the repeated dose toxicity/carcinogenicity studies showed any adverse effect on the reproductive organs.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Several repeated dose toxicity studies were conducted which cover the evaluation of potential toxic effects on the reproductive organs. The National Toxicology Program (1985) administered 1,2-dichlorobenzene by gavage for 13 weeks (0, 30, 60, 125, 250 or 500 mg/kg bw) and two years (0, 60 or 120 mg/kg bw) in male and female rats (F344) and mice (B6C3F1). All studies included the macroscopical and histopathological examination of prostate/testes or ovaries/uterus for all animals or control and high dose group respectively.

None of the studies showed any adverse effect on the reproductive organs. The only effects seen were interstitial-cell tumours of the testis in male rats with a significant positive trend when analyzed by the life-table test, but with a significant negative trend when analyzed by the Cochran-Armitage test. Since this tumour was not considered to be life threatening, the increase detected by the life-table test was discounted.

As confirmed by literature (Mangelsdorf et al. 2003, Ulbrich and Palmer 1995, Janer et al. 2007, Dent 2007, Sanbuissho et al. 2009) histopathological examinations of reproductive tissues in repeated dose toxicity studies on rodents are of high value and high sensitivity for evaluation of reproductive toxicity in males and females.

Applicant's summary and conclusion

Executive summary:

Several repeated dose toxicity studies were conducted which cover the evaluation of potential toxic effects on the reproductive organs. The National Toxicology Program (1985) administered 1,2-dichlorobenzene by gavage for 13 weeks (0, 30, 60, 125, 250 or 500 mg/kg bw) and two years (0, 60 or 120 mg/kg bw) in male and female rats (F344) and mice (B6C3F1). All studies included the macroscopical and histopathological examination of prostate/testes or ovaries/uterus for all animals or control and high dose group respectively.

None of the studies showed any adverse effect on the reproductive organs. The only effects seen were interstitial-cell tumours of the testis in male rats with a significant positive trend when analyzed by the life-table test, but with a significant negative trend when analyzed by the Cochran-Armitage test. Since this tumour was not considered to be life threatening, the increase detected by the life-table test was discounted.

As confirmed by literature (Mangelsdorf et al. 2003, Ulbrich and Palmer 1995, Janer et al. 2007, Dent 2007, Sanbuissho et al. 2009) histopathological examinations of reproductive tissues in repeated dose toxicity studies on rodents are of high value and high sensitivity for evaluation of reproductive toxicity in males and females.