Formic acid, manufacture of, by-products from

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Not specified if conducted to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Formic acid

EC Number:

200-579-1

EC Name:

Formic acid

Cas Number:

64-18-6

Molecular formula:

CH2O2

IUPAC Name:

formic acid

Details on test material:

- Name of test material (as cited in study report): Ameisensäure.
- Substance number: 78/651
- Source: Merck
- Analytical purity: min. 98%

Specific details on test material used for the study:

Name of test material (as cited in study report): Ameisensäure.
- Substance number: 78/651
- Source: Merck
- Analytical purity: min. 98%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: MUS RATTUS, Brunnthal
- Weight at study initiation: 185 +/- 15g
- Housing: routinely 3 animals/cage.
- Diet: complete diet ad libitum
- Water: tap water ad libitum


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

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: steel-glass whole body inhalation chamber
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: groups of 5 animals in wire mesh cages were exposed
- System of generating test atmospheres: a pump delivered test substance at constant rates to a glass evaporator heated to 40-70°C.
The vapor was diluted with fresh air before it entered the exposure chamber.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data


TEST ATMOSPHERE
- Brief description of analytical method used: air was abstracted with a tube at a rate of 5.4 L/min from the exposure chamber and guided through an IR photometer and then back to the inhalation chamber.
- Samples taken from breathing zone: yes



TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.82, 6.6, 8.08, 10.6, 14.7 mg/l (analytical)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs: Symptoms were observed during exposure and daily during the observation period.
Body weights were determined the day before treatment and weekly thereafter.
- Necropsy of survivors performed: yes

Statistics:

Probit analysis according to Finney (1971).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

7.4 mg/L air

Exp. duration:

4 h

Mortality:

There were no mortalities (0/20 exposed animals) at 2.8 mg/L. Mortality increased rapidly between 6.6 and 8 mg/L, and complete mortality was seen at 10.6 mg/L and above. All concentrations mentioned represent analytical results. The combined LC50 for male and female rats was 7.4 mg/L.

Clinical signs:

other: Closed lids, snout swiping, discharge from nose and eye, corrosion of nose and eyes, salivation, corneal opacity, loss of pain reflex, dyspnea, respiration sounds, flatulence, apathy, hunched posture, unsteady gait were seen in all treated groups. Symptom

Body weight:

Body weights were dose-dependently depressed in all survivors on day 7. Body weight gain was noted in the second week after treatment. The group at 8.08 mg/l did not reach the initial weight.

Gross pathology:

Dead animals: heart dilatation, hyperemic; lung: inflated.
Sacrificed animals: no findings.

Any other information on results incl. tables

Mortality

There were no mortalities (0/20 exposed animals) at 2.8 mg/L. Mortality increased rapidly between 6.6 and 8 mg/L, and complete mortality was seen at 10.6 mg/L and above. 

 

Dose   (mg/L; analytical)	mortalities/animals exposed
	males	females
2.82	0/10	0/10
6.60	2/10	1/10
8.08	8/10	810
10.60	10/10	10/10
14.70	10/10	10/10

 

The combined LC50 for male and female rats was 7.4 mg/L.

 

Applicant's summary and conclusion

Conclusions:

The clinical signs indicated corrosive properties of the test substance, evidenced by the occurrence of corneal opacity and corrosion of the dorsal nose in some cases. The symptoms persisted until termination 14 days after the rats were exposed to 6.6 mg/l or above.

There were no changes in animals that survived. Inflated lungs and dilated hearts were seen in animals that died.

Executive summary:

Conclusion

The LC50 (4h) was 7.4 mg/L in male and female rats. The clinical signs indicated corrosive properties of the test substance, evidenced by the occurrence of corneal opacity and corrosion of the dorsal nose in some cases. The symptoms persisted until termination 14 days after the rats were

exposed to 6.6 mg/l or above.

There were no changes in animals that survived. Inflated lungs and dilated hearts were seen in animals that died.