Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Remarks:
90 d-day study - A gross and histopathological examination was performed on all major organs inclusive reproductive organs/tissues (gonads, seminal vesicles, prostate, preputial or clitoral gland).
Type of information:
experimental study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Toxicity studies of 1,3-dichlorobenzene in Sprague-Dawley rats
Author:
McCauley PT, Robinson M, Daniel FB, and Olson GR.
Year:
1995
Bibliographic source:
Drug & Chem. Toxicol. 18, 201-221

Materials and methods

Principles of method if other than guideline:
Male and female Sprague-Dawley rats received 1,3-dichlorobenzene daily doses of 0, 9, 37, 147 or 588 mg/kg bw/day by corn oil gavage for 90 consecutive daily. All rats were observed daily for physiological and behavioral responses and for mortality. Body weights and food and water consumption were recorded weekly throughout the study. Blood samples were collected at necropsy for hematologic and serum chemistry measurements prior to necropsy. A gross and histopathological examination was performed on all major organs inclusive reproductive organs/tissues (gonads, seminal vesicles, prostate, preputial or clitoral gland).
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Reagent-grade 1,3-dichlorobenzene was obtained from Aldrich Chemical Company (Milwaukee, Wl).
Specific details on test material used for the study:
Purity > 99.99% (by GC/MS)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Purity > 99.99% (by GC/MS)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
One hundred animals were divided into five experimental groups consisting of 10 males and 10 females per group. There were four treatment Ieveis of 1 ,3-DCB [9, 37,
14 7, 588 mg/kg] and a vehicle control of corn oil. Individual animal dosages were determined weekly from individual body weights. Each rat received a dosing volume of 0.1 ml per 100 g of body weight. Animals were gavaged daily for 90 consecutive days.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Duration of test:
90 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 9, 37, 147 or 588 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
10 male and 10 female rats per dose
Control animals:
yes, concurrent vehicle
Details on study design:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI, USA
- Age of the animals when received in the testing laboratory: 70 days
- Weight at study initiation: 300-325 g (males); 225-250 g (females)
- Housing: Animals were used 2 per cage by sex in polycarbonate hardwood chip bedding (Absorb-Dri, Maywood, NY, USA)
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002 (Ralston-Purina Co., St. Louis, MO, USA) ad libitum
- Water (e.g. ad libitum): ad libitum
- Quarantine period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animals were held in a temperature controlled room
- Humidity (%): Animals were held in a humidity controlled room
- Photoperiod (hrs dark / hrs light): 12 hrs dark: 12 hrs light
Statistics:
Males and females were considered separately in all statistical analyses. A onefactor (dose) analysis of variance (ANOVA) was used to analyze normally distributed
measures: body weights, organ weights, organ weight ratios, food and water consumption, hematology and clinical chemistry.14 When a treatment effect was noted
(p <=0.05, F-test) the difference between the control and treatment groups was probed using Tukey's Multiple Comparison Procedure. For those hematological and clinical chemistry measures which were not normally distributed (extreme values, high variability), a nonparametric procedure, the Kruskai-Wallis test, was used to determine differences among the dose groups. lf a significant difference was reached (p <= 0.05), a Wilcoxon Rank Sum method was applied for multiple comparison of treatment groups. lncidence of histopathological lesions was analyzed by a Fisher Exact test, with a criterion of significance of P<= 0.05.

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
588 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects on reproductive organs were observed.

Observed effects

No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).

Any other information on results incl. tables

No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).

Applicant's summary and conclusion

Conclusions:
No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).
Executive summary:

Male and female Sprague-Dawley rats received 1,3-dichlorobenzene daily doses of 0, 9, 37, 147 or 588 mg/kg bw/day by corn oil gavage for 90 consecutive daily. All rats were observed daily for physiological and behavioral responses and for mortality. Body weights and food and water consumption were recorded weekly throughout the study. Blood samples were collected at necropsy for hematologic and serum chemistriy measurements prior to necropsy. A gross and histopathological examination was performed on all major organs inclusive reproductive organs/tissues (gonads, seminal vesicles, prostate, preputial or clitoral gland).

No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).