N,N-bis(2-methylpropyl)formamide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

exposure only at GD10 or GD10+11.

Data source

Reference

Reference Type:

publication

Title:

Embryotoxicity in Rats and Rabbits from Cutaneous Application of Amide-Type Solvents and Substituted Ureas.

Author:

Stula E.F. & Krauss W.C.

Year:

1977

Bibliographic source:

Toxicology and Applied Pharmacology 41, 35-55

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(2-methylpropyl)formamide

EC Number:

219-983-4

EC Name:

N,N-bis(2-methylpropyl)formamide

Cas Number:

2591-76-6

Molecular formula:

C9H19NO

IUPAC Name:

N,N-bis(2-methylpropyl)formamide

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): N,N-de(n-butyl)formamide
- Purity: Commercial grade with less than 2.0 % impurities.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 220 - 250 g
- Housing: Singly in suspended stainless steel wire sages
- Diet: Purina Laboratory Chow, ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: The test substance was applied on the intact skin over the thoracic vertebral area after the hair was removed with a hair clipper

TEST MATERIAL
- Amount(s) applied: Usually the volume of a single dose was less than 0.5 mL

Details on mating procedure:

No details given.

Duration of treatment / exposure:

The test item was applied to the skin of pregnant rats during the period of fetal organogenesis.

Frequency of treatment:

On day 10 or at day 10 + 11 of gestation.

Duration of test:

20 days

Doses / concentrations

Remarks:

Doses / Concentrations:
On day 10 of gestation: 600 mg/kg and 1200 mg/kg; On day 10 + 11 of gestation: 600 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5 - 9 (see table 1 under "Any other information on results incl. tables")

Control animals:

yes

Examinations

Maternal examinations:

- Body weight change
- Approximate lethal dose (ALD)

Ovaries and uterine content:

In addition to gross examination of fetuses and uteri, the following determinations were recorded:
- number of live fetuses
- number of dead fetuses
- number of implantation sites
- number of resorption sites

Fetal examinations:

- fetal weight
- fetal crown-rump length
- 2/3 of the fetuses from each litter were stained with alizarin red for detection of skelatal abnormalities.
- The remaining fetuses were fixed in Bouin's fluid and examined for visceral abnormalities.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
- Approximate lethal dose: 1500 mg/kg

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
- Embryomortality was found only at a level in rats that was lethal for the mother (33 % embryomortality at a dose of 1200 mg/kg)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Table 1: Embryotoxic effects of the test item applied to skin of pregnant rats

Number of pregnant rats in group	Daily dose [mg/kg]	Gestation days applied	48-h Mother body weight change (%)	Embryomortality (%)	Average fetal weight (g)	Fetal abnormalities
9	600 H2O Control	10	+2^b	7	2.6	-
8	600 (1/2)	10	0^b	7	2.5	-
4^a	1200 (1/1)	10	-5^b	33	2.7	-
6	600 H2O Control	10 + 11	+3	9	2.1	-
5	600 (1/2)	10 + 11	-4	8	1.6	-

^anot included were 1/5 pregnant mothers that died; 3/3 nonpregnant females survived this dosage

^b24-h mother body weight change