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Toxicity to reproduction

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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

Constituent 1
Chemical structure
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.