Propyl chloroformate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD 401 with neligabgle restrictions mostly due to reduced reporting in times before GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Propyl chloroformate

EC Number:

203-687-7

EC Name:

Propyl chloroformate

Cas Number:

109-61-5

Molecular formula:

C4H7ClO2

IUPAC Name:

propyl carbonochloridate

Details on test material:

- Name of test material (as cited in study report): n-Propylchlorkohlensaeureester
- Physical state: liquid
- Analytical purity: not reported
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hagemann + Wiga
- Mean weight per group at study initiation: 190-240 g (male); 160-180 g (females)
- Fasting period before study: 15 -20 h
- Diet (e.g. ad libitum): Merilan MRH-Haltung; Eggersmann KG


ENVIRONMENTAL CONDITIONS
not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.93; 2.0; 2.9; 13.6; 20.0; 29.4; 43.0; 63.2

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg eaquals ca. 1.2 ml/rat

Doses:

3160.0; 2150.0; 1470.0; 1000.0; 681.0; 147.0; 100.0; 46.4 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mean body weight and observation of clinical signs was performed several times on the day of administration and once daily afterwards with the except on weekends and on holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

according to Finney, D.J., Probit Analysis, Cambridge University Press, 3rd edition, 1971

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 210 mg/kg bw

95% CL:

1 055.4 - 1 391.3

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 1 000 - < 1 500 mg/kg bw

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 100 mg/kg bw

95% CL:

741.5 - 1 546.6

Mortality:

46.4 mg/kg: no mortality observed
100 mg/kg: no mortality observed
147 mg/kg: no mortality observed
681 mg/kg: 1/5 females died within 2 d; no mortality observed in males
1000 mg/kg: 1/5 females died within 1 d; no mortality observed in males
1470 mg/kg: 4/5 females died within 1 d; 5/5 males died within 1 d
2150 mg/kg: 10/10 animals died within 1 d
3160 mg/kg: 10/10 animals died within 1 d

Clinical signs:

other: 46.4 mg/kg: no treatment related effects 100 mg/kg: no treatment related effects 147 mg/kg: aggressiveness 681 mg/kg: dyspnoea, stertor (respiratory noise), apathy, staggering, tremors, piloerection, salivation, poor general state 1000 mg/kg: dyspnoea, ap

Gross pathology:

Animals that died:
Heart: acute dilatation on the right side; acute passive hyperemia; stomach: necrotic white mucosa (necrotic corrosive gastritis); intestines: necrotic white mucosa (necrotic corrosive gastritis)
Sacrificed animals:
46.4 - 147 mg/kg: Organs: no abnormalities detected
1000 and 1470 mg/kg: Forestomach: diverticularization, in some cases with scabs/crusts and in some cases adhesions between the forestomach and spleen, liver and peritoneum

Applicant's summary and conclusion

Executive summary:

The study is comparable to OECD 401 with acceptable restrictions mostly due to reduced reporting in times before GLP. Groups of 5 rats per sex and dose were administered 46.4, 100, 147, 681, 1000, 1470, 2150 and 3160 mg/kg of the test substance.

The acute LD50 for female rats is 1210 mg/kg (males & females) after oral application (males: 1000 - 1500 mg/kg; females: 1100 mg/kg). No mortality was observed at doses up to 147 mg/kg. Mortality and dyspnoea, apathy, staggering, piloerection and general poor state were observed as main clinical signs in treatments of 681 mg/kg and higher. In died animals, acute heart dilatation on the right side, acute passive hyperemia, necrotic white mucosa in stomach and intestine was observed.