N,N-dibutylformamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01.03.1989 - 04.04.1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24.02.1987, before latest revision 9 Oct 2017.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Version / remarks:

November 1984

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dibutylformamide

EC Number:

212-090-0

EC Name:

N,N-dibutylformamide

Cas Number:

761-65-9

Molecular formula:

C9H19NO

IUPAC Name:

N,N-dibutylformamide

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: 230688
- Expiration date of the lot/batch: 06.08.1989
- Purity test date: 97.0%
- slightly viscous, transparent liquid


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: under light closure at room temperature

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Bot:WISW (SPF-CPD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Paderborn
- Age at study initiation: male 9 weeks, female >= 16 weeks
- Weight at study initiation: male 211 - 231 g, female 219 - 233 g
- Housing: Makrolon cages Type III, during testing Makrolon cages Type II;
wooden granules Type S 8/15, Rettenmaier & Son
- Historical data: available
- Diet: Altromin 1324 ad libitum
- Water ad libitum:
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 2° C
- Humidity (%): ca. 50
- Air changes (per hr): 10 per hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: cellulose unspecified

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
male 500 mg/kg Kgw.3.57 - 3.77 mg/cm2
1000 mg/kg Kgw.:7.03 - 7.40 mg/cm2
female 500 mg/kg Kgw.:3.70 - 3.87 mg/cm2
1000 mg/kg Kgw.: 7.47 - 7.77 mg/cm2

- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

500, 710, 1000 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: daily
- Necropsy of survivors performed: yes
- Clinical signs including body weight day 4, day 8 and then weekly
- Other examinations performed: clinical signs, body weight, histopathology.
behavior, nwervous system, posture,

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 790 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 730 mg/kg bw

Based on:

test mat.

Mortality:

500 mg/kg: no mortalityy
710 mg/kg 1 male and 2 female
1000 mgL/kg: 5 male and 5 female

Clinical signs:

other: Apathy, difficult breathing, decreased motility, partly tumbling gait, low reflexes, occasionally shaved fur, salivation and spread posterior extremities Only female animals: erythema, brown discolouration, scabbing, hardening and incrustations.

Gross pathology:

Blown lungs, partially dark, spotty, liver partly pale, dark, single spleen partly pale, kidneys partly pale, bladder bulging with partly
bloody urine filled and occasionally ulcer-like ffoci in the glandular stomach.

Any other information on results incl. tables

Table 1: Results of acute dermal toxicity study in rats

Group	Dose (mg/kg bw)	Toxicol. results*	Duration of signs	Time of death	Mortality (%)
rat - male
1	500	0/5/5	2h - 2d	--	0
2	710	1/5/5	2h - 3d	5h	20
3	1000	5/5/5	2h - 1d	5h - 1d	100
rat - female
1	500	0/5/5**	2h - 4d	--	0
2	710	2/5/5**	45´ - 8d	7h	40
3	1000	5/5/5**	40´ - 2d	1d - 2d	100

* No. of dead animals/animals with symptoms/animals treated

** Dermal findings were not considerd in this table.

LD50, rat - male: ca. 790 mg/kg bw

LD50, rat - female: ca. 730 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The study on acute dermal toxicity of N,N-Dibutylformamide in rats resulted in a LD50 value of 790 mg/kg for male animals and 730 mg/kg for female animals, A classification according to the CLP Regulation (EC) No. 1272/2008 (EU-GHS: Cat. 3) is required.

Executive summary:

In a study according to OECD 402 the unchanged test item was applied on the back of male and female Wistar rats for 24 hours under occlusive conditions. Three doses were tested, 500, 710 and1000 mg/kg bw. Following application, the animals were observed for a period of 14 days and clinical signs and body weight was recorded. All doses tested resulted in symptoms; apathy, difficulty breathing, reduced motility, sometimed tumbling gait, slight reflexes and occasionally dusty fur, salivation and spreas extremities. The effect started later about 1 to 2 hours and disappeared on the second, at the latest of the 8th day of the study. Ihe lowest dose used females showed skin symptoms like reddening, brown discoloration, scrabbing, hardening and crusting. Death occured in both sexes from 710 mg/kg bw on. The LD50 for males was 790 mg/kg and females was 730 mg/kg

Regarding the results of the dermal test classification according to Regulation (EC) No.1272/2008 (EU-GHS: Cat. 3) is required.