(Z)-1,3-dichloropropene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 November 1988 to 23 December 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted to an appropriate test guideline with no or minor deviations.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

1

Reference substance name:

(Z)-1,3-dichloropropene

EC Number:

233-195-8

EC Name:

(Z)-1,3-dichloropropene

Cas Number:

10061-01-5

Molecular formula:

C3H4Cl2

IUPAC Name:

1,3-dichloroprop-1-ene

Specific details on test material used for the study:

Analysis: 94.51-97.51% cis isomer with 1.5% trans isomer
Stability: stable for the duration of the study (no changes from 21 Nov1988 to 19 Jan 1989
Used undiluted in oral test

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Fischer 344 rats aged 8-9 weeks were obtained from Charles River U.K. Ltd. On arrival they were housed in single sex groups of up to 12 rats to a cage. The animals were quarantined for a minimum of five days in a non-barriered animal room with access restricted to essential personnel. At least five days before dosing the animals were rehoused (as single sex groups of up to four rats) in cages with stainless steel wire-mesh walls, floors and tops. Each cage measured 38 cm x 25 cm x 18 cm. Paper-lined trays for excreta were placed beneath each cage and changed three times weekly. A pelleted diet (PRD, Labsure Animal Foods) and water from the public supply were provided ad libitum. There were no excursions of animal room environmental
conditions beyond target values of 19° to 23°C and 30% to 70% R.H. that were considered to have influenced the outcome of the study. Lighting (fluorescent tubes) was automatically controlled to provide a 12 hour day and 12 hour night. Animals assigned to the study were identified by cage-labels displaying the animal numbers, experiment number, sex and dose-level and by ear-notches denoting the animal number.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Single dose by gavage.

Doses:

38, 51, 68, 90, 120, 160, or 213 mg/kg bodweight

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

Groups of five male and five female rats were fasted overnight, weighed and given a single dose of the test material by gavage, using a ball pointed cannula and syringe. Approximately three hours after dosing on Day ). the animals were allowed food again ad libitum.

A careful clinical examination was made up to three times daily for the first three days and once daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 bodyweights were recorded, and changes in bodyweight calculated.

All animals were subject to necropsy. Animals surviving to the end of the study were killed by an intraperitoneal injection of sodium pentobarbitone. The cranial, thoracic and abdominal cavities and viscera were examined and any gross pathological changes recorded.

Statistics:

The 14 day LD50, 95% confidence limit, and dose morality slope were calculated using a method based on probit analysis (Finney 1977)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

93 mg/kg bw

95% CL:

76 - 113

Remarks on result:

other: slope = 6.4

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

78 mg/kg bw

95% CL:

68 - 90

Remarks on result:

other: slope not estimated

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

85 mg/kg bw

95% CL:

76 - 96

Remarks on result:

other: slope = 8.7

Mortality:

Mortalities occurred on days 1,2, and 3. Only 3 rats survived treatment at 90 mg/kg and above; the majority of deaths occurred within 4 hours of dosing.

Clinical signs:

other: Common signs of reaction to treatment observed among rats dosed at 38, 51, or 68 mg/kg were limited to voiding of soft faeces or diarrhoea within 4 hrs of dosing and piloerection and/or unkempt appearance druing day 2. Recovery of surviving rats was comp

Gross pathology:

Principal abnromalities found in decedents were abnormal contents, inflammation and haemorrahage of the stomach, darkening of the liver, lung congestion and discolouration of the renal medulla. No macroscopic abnormalities were found in surving animals.

Any other information on results incl. tables

Mortality following acute oral adminstration of test material
Dose	M	F	M/F
38	0/5	0/5	0/10
51	0/5	0/5	0/10
68	0/5	0/5	0/10
90	3/5	5/5	8/10
120	5/5	5/5	10/10
160	4/5	5/5	9/10
213	5/5	5/5	10/10

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of the undiluted in test material in rats (males and females combined) was 85 mg/kg body weight (95% confidence interval 76-96 mg/kg).
LD50 of males only was 93 mg/kg (76 to 113 mg/kg 95% CI)
LD50 of females only was 78 mg/kg (68 to 90 mg/kg 95% CI)

Executive summary:

A GLP Compliant acute oral toxicity study has been completed in accordance with OECD Guideline 401. The acute oral LD50 of the undiluted in test material in rats was 85 mg/kg body weight (95% confidence interval 76-96 mg/kg).

LD50 of males only was 93 mg/kg (76 to 113 mg/kg 95% CL)

LD50 of females only was 78 mg/kg (68 to 90 mg/kg 95% CL)