N,N-dibutylformamide

Endpoint summary

Description of key information

oral: LD50 = 1050 mg/kg bw (rat)

inhalative: no death observed under saturated atmosphere (rat)

dermal: LD50 male animals 790 mg/kg ; female; 730 mg/kg (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight: males 205 g, females 163 g
The animals were offered a standardized animal laboratory diet.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

0.5% aqueous CMC preparation
Test concentrations used were 2.15, 3.16, 4.64, 6.81, 10, 12.1, 14.7, 21.5% (G/V).

Doses:

215, 316, 464, 681, 1000, 1210, 1470, 2150 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
- Application volume: 10 mL/kg

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 050 mg/kg bw

Based on:

test mat.

Mortality:

215, 316 and 464 mg/kg bw: no deaths after 14 days
681 mg/kg bw: 1/10 after 14 days
1000 mg/kg bw: 2/10 after 14 days
1210 mg/kg bw: 9/10 after 14 days
1470 and 2150 mg/kg bw: 10/10 after 14 days

Clinical signs:

other: Time of deaths on the first study day. Staggering, atony, narcotic-like state with missing pain and corena reflex, spastic gait, partly salivation and lachrymation.

Gross pathology:

Animals that died:
- heart: acute congestion, acute congestive hyperemia
- lung: manifold slight edematized
- liver: manifold disseminated lobule periphery;
- stomach: partly substance-induced mucosa malacia
- intestine: partly atonic, diarrheic content.

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 050 mg/kg bw

Quality of whole database:

BASF-internal standard test

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

according to H.F. Smyth et al., Am. Ind. Hyg. Ass. J. 23, 95 - 107 (1962)

GLP compliance:

no

Test type:

other: inhalation hazard test

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weight: males 194 g, females 163 g

Route of administration:

inhalation: vapour

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

7 h

Concentrations:

0.2 mg/L

No. of animals per sex per dose:

12 (sex not specified)

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology: heart, lung, trachea, liver, spleen, kidney, central nervous system, lymph node system

Sex:

not specified

Dose descriptor:

discriminating conc.

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: saturated atmosphere

Mortality:

None

Clinical signs:

other: None

Gross pathology:

Nothing abnormal detected.

Other findings:

- Histopathology: No findings

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24.02.1987, before latest revision 9 Oct 2017.

Deviations:

no

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

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

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

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,

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 790 mg/kg bw

Based on:

test mat.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

730 mg/kg bw

Additional information

Oral

A study similar to OECD TG 401 was performed and the test item was applied orally to male and female Sprague-Dawley rats. The following doses were tested: 215, 316, 464, 681, 1000, 1210, 1470, 2150 mg/kg bw. Five animals per sex per dose were administered via gavage and observed for a period of 14 days. Clinical signs and body weight was recorded. Necropsy of the survivors was performed. No deaths were reported for the 215, 316 and 464 mg/kg bw dose groups after 14 days. One death was reported after dosing of 681 mg/kg bw and two death animals were reported after dosing 1000 mg/kg bw. For the 1210 mg/kg bw dose group 9 death animals were observed and for the highest dose levels of 1470 and 2150 mg/kg bw all animals died during the observation period. Only unspecific signs of toxicity were observed during clinical examination and in gross pathology . The LD50 was 1050 mg/kg bw for males and females rats (1979, reliability score: 2).

Inhalation

In an inhalation hazard test male and female rats were exposed to vapors of the test item at a concentration of 0.2 mg/L for 7 hours. The test was performed according H.F. Smyth et al. (Am. Ind. Hyg. Ass. J. 23, 95 - 107 (1962). Following administration, the rats were observed for a period of 14 days for clinical signs. Necropsy of the survivors was performed and histopathology of heart, lung, trachea, liver, spleen, kidney, central nervous system, and lymph node system. No clinical signs, mortality or anything abnormal was detected (1979, reliability score: 2).

Dermal

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 and 1000 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; apthy, difficulty breathing, reduced motility, sometimed tumbling gait, slight reflexes and occasionally dusty fur, salivation and spreas extremities. The effect started ater about 1 to 2 hours and disappeared on the second, at the latest of the 8th day of the study. At the 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.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute oral toxicity Cat.4 (H302:" Harmful if swallowed"), as amended for the tenth time in Regulation (EU) No 2017/776. Regarding the results of the dermal study classification is required; dermal toxicity Cat.3 (H311 :Toxic in contact with skin). The substance is not considered to be classified for inhalatory toxicity.