N-methylformamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study with acceptable restrictions (no details about the test substance; only 2 dose levels tested [at least 3 recommended], post exposure period 7 [low dose] and 12 days [high dose]).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

monomethylformamide

IUPAC Name:

monomethylformamide

Details on test material:

no details

Test animals

Species:

rabbit

Strain:

Vienna White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: M.GAUKLER, Offenbach, Germany
only healthy animals (no skin lesions)
Mean initial weight of males: 2.3 kg; females 2.6 kg
Certified diet and tap water ad libitum
no further details

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Fur removed by clipping 15-24 h prior to application.
Exposure area appr. 220 cm²
After application test area covered by inert foil plus fixation via bandage.
After 24 h exposure test site washed with luke warm water and dried.

Duration of exposure:

24 h

Doses:

400 or 2000 mg/kg bw

No. of animals per sex per dose:

5 at 2000 mg/kg bw and 10 at 400 mg/kg bw

Control animals:

not required

Details on study design:

Clinical signs and local effects recorded (no details about frequency).
No data about body weight.
Post exposure period 12 days (high dose) or 7 days (low dose).
Necropsy performed.

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 289 mg/kg bw

Remarks on result:

other: Probitanalysis according to Finney

Mortality:

Data on mortality are presented in the Table below. At the low dose 2 females died due to pneumonia; these deaths might be not treatment related (not discussed by the authors). Lethal effects mainly within 48 h after application.

Clinical signs:

other: 2000 mg/kg bw: apathy, increased respiration rate, tremor, convulsions. No effects found 8 days after application. 400 mg/kg bw: no symptoms.

Gross pathology:

Animals found dead: acute dilatation of the heart, hyperemia, liver lobules greyish.
Survivors: no treatment related effects.

Other findings:

Local effects:
400 & 2000 mg/kg bw: slight reddening which was reversible within the post exposure observation period

Any other information on results incl. tables

Mortality in rabbits after acute dermal exposure to N-methylformamide

Dose in mg/kg bw	Mortality within
	1 h	24 h	48 h	7 days	12 days
2000	0/5m 0/5f	0/5m 0/5f	1/5m 4/5f	1/5m 4/5f	2/5m 4/5f
400	0/10m 1/10f	1/10m 2/10f*	1/10m 2/10f*	1/10m 2/10f*	No data

m: males; f: females

*: animals died due to pneumonia

Applicant's summary and conclusion

Conclusions:

The dermale LD50 in rabbits was 1289 mg/kg bw for males and females combined, as there are no indications for gender-specific differences in susceptibility.

Executive summary:

Comparable to Guideline study with acceptable restrictions (no details about the test substance; only 2 dose levels tested [at least 3 recommended], post exposure period 7 [low dose] and 12 days [high dose]).

Five male and 5 female White Vienna rabbits received dermal applications of 2000 mg/kg bw undiluted test substance (occlusive, exposure period 24 h followed by washing; post exposure period 12 days). Using the same experimental design but 7 days post exposure period a lower dose of 400 mg/kg bw was tested in 10 males and 10 females. Animals died within 48 h after application (with one exception at the high dose level, died within 12 days). No clinical signs were detected at the low dose. At 2000 mg/kg bw apathy, increased respiration rate, tremor, and convulsions were observed. Local effects were restricted to a slight reddening which was reversible. Necropsy revealed not treatment related effects in survivors but dilatation of the heart, hyperemia and greyish liver lobules in animals found dead. Two rabbits of the low dose group died due to pneumonia (probably not treatment related).

Conclusion: The dermale LD50 in rabbit was 1289 mg/kg bw for males and females combined, as there are no indications for gender-specific differences in susceptibility.