N,N-dimethylbutylamine

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, well documented and acceptable for assessment, males were exposed only 6 weeks prior to mating compared to the 10 weeks recommended by the guidelines 415 and 416 but sufficiently long enough if compared to the screening test (guideline 421) which recommends only 2 weeks of exposure prior to mating. Older male rats were used as can be extrapolated from the initial body weights whereas younger rats are recommended in the guidelines.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1989

Materials and methods

Principles of method if other than guideline:

Two concentrations of butan-1-ol (3000 and 6000 ppm) were administered by inhalation to separate groups of 15 pregnant Sprague-Dawley rats for 7 hr per day throughout gestation ; 18 male rats were similarly exposed for 7 hr per day for 6 weeks, and mated to unexposed females.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butan-1-ol

EC Number:

200-751-6

EC Name:

Butan-1-ol

Cas Number:

71-36-3

IUPAC Name:

butan-1-ol

Details on test material:

- Name of test material (as cited in study report): 1-butanol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: (P) Males: mean: 429-512 g; Females: mean: no data


ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

not specified

Vehicle:

other: air

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentrations measured in the exposure chambers approximated the target concentrations of 3000 and 6000 ppm. Mean (±s.d.) 1-butanol concentrations were 3010 (±50) and 6000 (±80) ppm, and results of periodic confirmatory charcoal tube samples were 3000 (± 90) and 5960 (± 110) ppm, respectively .

Duration of treatment / exposure:

females: Exposure period: day 1 - 20 of gestation
males: 6 weeks before mating

Frequency of treatment:

7 h/d

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 3000, 6000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

15 females per dose
18 males per dose

Control animals:

yes

Examinations

Statistics:

Data were analyzed using multivariate analysis of variance (MANOVA) on tests with multiple dependent measures, followed by analysis of variance (ANOVA) on each dependent variable if a significant MANOVA was observed. If only one dependent variable was obtained, ANOVA was used, followed by the Tukey Range Test to determine which cell means differed from one another.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

18.5 mg/L air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observed

Results: F1 generation

Effect levels (F1)

Dose descriptor:

other: NOAEL developmental neurotoxicity

Generation:

F1

Effect level:

18.5 mg/L air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observrd

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

No general maternal or paternal toxicity was reported. Paternal exposure had no detectable effect on pregnancy rate in non-exposed females; maternal exposure was also without detectable effect on pregnancy rate. Although the study was designed to provide animals for postnatal assessment of developmental neurotoxicity, the lack of effect on pregnancy rate following either maternal or paternal exposure suggested that butan-1 -ol had no effect on fertility up to 6000 ppm. In the 6000 ppm group, 4 of the 78 (5%) behavioural measures, and 4 of the 64 (6%) neurochemical measures differed from those of controls.

There was no discernible pattern of effects.