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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from authoritative database

Data source

Referenceopen allclose all

Reference Type:
other: authoritative database
Title:
Sub-chronic study for 1,2 dichloropropane in rats by oral gavage.
Author:
U.S. National Library of Medicine
Year:
2017
Bibliographic source:
HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2017.
Reference Type:
secondary source
Title:
Sub-chronic study for 1,2 dichloropropane in rats by oral gavage.
Author:
OECD SIDS,SIAM17
Year:
2003
Bibliographic source:
Sub-chronic study for 1,2 dichloropropane in rats by oral gavage, OECD SIDS,SIAM17, 2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
To evaluate the toxic nature of 1,2 dichloropropane in male and female Fischer 344 rats by oral gavage for 13 weeks.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1,2 dichloropropane
- Molecular formula ;C3H6Cl2
- Molecular weight ;112.986
--Purity;99.9%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animal
TEST ANIMALS
- Age at study initiation: 7-8 wk

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Details on oral exposure
PREPARATION OF DOSING SOLUTIONS:


VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0, 60, 125, 250, 500 or 1000
mg/kg bw/day
- Amount of vehicle (if gavage):
- Lot/batch
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentration of test article in the dosing solutions was verified using GC-FID. GC analysis of the dosing solutions demonstrated that the achieved concentration was 95 - 100% of target.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days/wk for 13 wk
Doses / concentrations
Remarks:
0, 60, 125, 250, 500 or 1000 mg/kg bw/day
No. of animals per sex per dose:
Total no. of animals 120
0 mg/kg bw/day -10 male and 10 female animals
60 mg/kg bw/day -10 male and 10 female animals
125 mg/kg bw/day -10 male and 10 female animals
250 mg/kg bw/day -10 male and 10 female animals
500 mg/kg bw/day -10 male and 10 female animals
1000 mg/kg bw/day -10 male and 10 female animals
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified

Examinations

Observations and examinations performed and frequency:
Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily. Each animal was given a detailed weekly examination, including palpation for tissue masses or swelling

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified

- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified


OPHTHALMOSCOPIC EXAMINATION: Not specified


HAEMATOLOGY: Not specified

CLINICAL CHEMISTRY: Not specified


URINALYSIS: Not specified


NEUROBEHAVIOURAL EXAMINATION: Not specified
Sacrifice and pathology:
Sacrifice and pathology
GROSS PATHOLOGY: Yes , Necropsies were performed on all surviving animals at the end of the treatment period.
HISTOPATHOLOGY: Yes , A comprehensive range of tissues were sampled and preserved, and those from the controls, 500 mg/kg and 1000 mg/kg groups
subject to Microscopic examination.
Statistics:
Mean ± Standard deviation was observed.

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
All male and female rats given 1000 mg/kg bw/day and 5/10 males from the 500 mg/kg bw group died before necropsy. All animals from the other treatment groups survived until study termination
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Final mean body weights were decreased 16% in male and 8% in females given 500 mg/kg bw/d of treated group compare to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
The liver was the only organ to be affected by treatment, with centrilobular congestion present in 5/10 males and 2/10 females given 1000 mg/kg bw/day of treated group compare to control.
Hepatic fatty change and centrilobular necrosis were observed in 2/10 females from the 1000 mg/kg bw/day of treated group compare to control.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
250 other: mg/kg/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No statistically significant effects were observed in clinical sign, body weight, gross pathology and histopathology
Remarks on result:
other: No toxic effect observed

Target system / organ toxicity

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 250mg/kg/day in male and female Fischer 344 rats by oral gavage for 13 weeks for 1,2 dichloropropane(978-87-5).
Executive summary:

2 dichloropropane was assessed for its possible toxic effect .For this purpose subchronic study was conducted in male and female Fischer 344 rats by oral gavage for 13 weeks. The test substance was exposed to the animals at the dose concentration of0, 60, 125, 250, 500 or 1000 mg/kg bw/day by using corn oil as vehicle. The animals were observed for Mortality, clinical sign, Body weight, gross pathology and Histopathology.All male and female rats given 1000 mg/kg bw/day and 5/10 males from the 500 mg/kg bw group died before necropsy. All animals from the other treatment groups survived until study termination.No statistically significant effects were observed.All male and female rats given 1000 mg/kg bw/day and 5/10 males from the 500 mg/kg bw/day group died before necropsy. All animals from the other treatment groups survived until study termination. Significant effect were observed at the body weight and the histopatholgy of the liver at the dose group of 500 mg/kg/day of trated group compare to control. No significant effectwere observed at 250 mg/kg bw/day . Therefore NOAEL was considered to be 250 mg/kg bw/day for2 dichloropropane in male and female Fischer 344 rats by oral gavage for 13 weeks.Significant effect were observed at the body weight and the histopatholgy of the liver at the dose group of 500 mg/kg/day of trated group compare to control. No significant effectwere observed at 250 mg/kg bw/day . Therefore NOAEL was considered to be 250 mg/kg bw/day for2 dichloropropane in male and female Fischer 344 rats by oral gavage for 13 weeks.