2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride

Repeated dose toxicity: oral

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

Reference

Reference 1

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 2

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

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

Test material information

Constituent 1

Reference substance name:

1,2-dichloropropane

EC Number:

201-152-2

EC Name:

1,2-dichloropropane

Cas Number:

78-87-5

Molecular formula:

C3H6Cl2

IUPAC Name:

1,2-dichloropropane

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 or test system 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.