4-tert-butylcyclohexyl chloroformate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD 403 with acceptable restrictions mostly due to reduced documentation (e.g. only mean body weights are reported) and no 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 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylcyclohexyl carbonochloridic acid ester

IUPAC Name:

4-tert-butylcyclohexyl carbonochloridic acid ester

Constituent 2

Reference substance name:

77/808

IUPAC Name:

77/808

Details on test material:

- Name of test material (as cited in study report): 4-tert.-ButylcyclohexylchlorKohlensäureester ( 4-tert-butylcyclohexyl carbonochloridic acid ester)
- Physical state: clear liquid
- Analytical purity: 98 %
- 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: Breeder MUS RATTUS, Brunntahal (Germany)
- Weight at study initiation: males: 187 +/- 4; females: 185 +/- 5

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals are fixed in class tubes with their snout produding into the inhalation chamber
- System of generating particulates/aerosols: The test atmospere was generated by mixing a continious flow (infusion pump) ot the test substance liquid with compressed air (1.5 bar) employing a jet nozzel.

TEST ATMOSPHERE
- Brief description of analytical method used: The test substance in the test atmosphere was traped in 35 g ethanol. The chlorformate was than hydrolized and the delibarated chloride ions were electrochemical determinded (electrode).
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3.58; 1.18, 1.09; 0.88; 0.72 mg/l (measured)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Weighing at the beginin, after 7 days and after 14 days
Observations: several times at the day of exposure, once daily afterward except week end and holydays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mean body weight (per dose and sex)

Statistics:

The LC 50 value was calculated by probit analysis

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.72 - < 0.88 mg/L air

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

> 0.72 - < 0.88 mg/L air

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

0.93

95% CL:

0.84 - 1.02

Exp. duration:

4 h

Mortality:

Mortality was observed (see Remarks)

Clinical signs:

other: At 0.88 to 3.58 mg/l/4h attempts to escape, salivation dyspnoea, anaemic pallor, apathy, red discharge from eyes and nose, alopecia wer recorded At 0.72 mg/l/4h: dyspnoea, red discharge from eyes and nose and smeared fur were observed The surviving anima

Body weight:

Body weight gain of all surviving animals was positive at the termination of the study

Gross pathology:

sacreficed animals: no substance related obsevation
animals died: haemorhagic lung, lung edema, reddening of the nasal mucosa

Any other information on results incl. tables

Mortality

Concentration mg/l		male	female
analytical	nominal
3.58	19.6	10/10	10/10
1.18	3.43	10/10	9/10
1.09	5.39	10/10	8/10
0.88	2.25	10/10	5/10
0.72	1.18	0/10	0/10

Applicant's summary and conclusion

Executive summary:

The study is comparable to OECD 403 with acceptable restrictions mostly due to reduced documentation (e.g. only mean body weights are reported) and no GLP. Animals tried to escape from exposure. Salivation dyspnoea, anaemic pallor, apathy, red discharge from eyes and nose and alopecia were observed. Animals that died after exposure died with in the first 24 h and showed haemoragic and edematous lungs at necropsy. The animals recovered completely within 9 days. There was no finding at necropsy at the termination of the study.

Conclusion

A LC50 value of >0.72 - < 0.88 mg/l/4h for tert-Butylcyclohexyl-chlorformate aerosol was determined in this study. The substance therefor is classified as toxic after inhalation.