sec-butylamine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study with well-documented methodology

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Version / remarks:

note: not mentioned in ACC IUC5

Deviations:

yes

Remarks:

Food consumption was not measured, while a deviation from standard reproductive toxicity testing, considered an acceptable deviation.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isopropylamine

EC Number:

200-860-9

EC Name:

Isopropylamine

Cas Number:

75-31-0

Molecular formula:

C3H9N

IUPAC Name:

propan-2-amine

Details on test material:

- Name of test material (as cited in study report): Isopropylamine (2-aminopropane)
- Substance type: organic
- Physical state: clear liquid
- Analytical purity: 99.77 %
- Lot/batch No.: LP-606

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

- Age (males): 10 weeks
- Weight at day 0 of gestation (females): 214-282 g
- Weight at day 0 of gestation (males): 317-389 g
- Number of animals: 25 females/group
- Thirty air changes per hour

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Details on exposure:

days 6-15 of gestation

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Method: Gas analyser
- Sampling time: at least 5 times/day (treatment); the control was checked for the presence of test material
twice during the study

Details on mating procedure:

- Mating: 1 female / 1 male
- Day 0 of gestation: presence of vaginal plug

Duration of treatment / exposure:

- Gestation days 6-15

Frequency of treatment:

- Six hours per day

Duration of test:

- Twenty days, Cesarean section on gestation day 20

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/m³ air (analytical)

Doses / concentrations 2

Dose / conc.:

499 mg/m³ air (analytical)

Doses / concentrations 3

Dose / conc.:

1 000 mg/m³ air (analytical)

No. of animals per sex per dose:

25 females/group

Control animals:

yes

Details on study design:

rat (Sprague-Dawley)
inhalation: vapour (whole body)
50, 500, 1000 mg/m3 (nominal conc.)
50, 499, and 1000 mg/m3 (analytical conc. (stable and homogeneous (within 4% difference between chamber locations)))
Vehicle: air
Exposure: - Gestation days 6-15 (- Six hours per day)
equivalent or similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Examinations

Maternal examinations:

- Mortality: twice daily
- Clinical observations: on gestation days 0 and 6-20 (on treatment days after exposure)
- Body weight gain: gestation days 0, 6, 10, 13, 16 and 20
- Food consumption: not measured

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Macroscopy: findings dams recorded
- Microscopy: not performed

Ovaries and uterine content:

- Examination of uterine content: number of corpora lutea; relative position and number of live and dead foetuses and early and late resorptions

Fetal examinations:

- Examination of fetuses: sex; weight; external, visceral (1/2 of each litter) and skeletal (1/2 of each litter) findings

Statistics:

- Dunnett's test; Mann-Whitney U test; Fisher's Exact test

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
- Mortality and day of death: no deaths
- Body weight(gain): decreased at 1000 mg/m3 on gestation days 10, 13, 16 and 20 and during day 6-20;
at 500 mg/m3, lower gains during gestation days 6-10 and overall 6-20
- Number early delivery: 1 female at 500 mg/m3
- Number of resorptions (early/late): at 500 mg/m3: slightly increased (1.0/dam vs 0.6/dam in the control)
- Number of implantations: no differences
- Pre and post implantation loss: Pre-implantation loss no differences; post-implantation loss, at 500 mg/m3
slightly increased (1.0/dam vs 0.6/dam in the control)
- Number of corpora lutea: no differences
- Duration of pregnancy: scheduled sacrifice on gestation day 20
- Gross pathology incidence and severity: at 1000 mg/m3: reduced abdominal fat in 9 females;
at 50 mg/m3: reduced abdominal fat in 2 females
Incidental hydronephosis, kidney stones and dilated ureter were observed without relationship to treatment.
- Organ weight/histopathology: no da
- Clinical signs: at 1000 mg/m3: rales, laboured breathing and vaginal discharge (one female). An increased
incidence of sneezing, fur staining/encrustration and nasal discharge;
at 500 mg/m3: an increased incidence of sneezing
- Number mated/pregnant at 0, 50, 500 and 1000 mg/m3: 25/22, 25/25, 25/24, 25/24

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEC

Effect level:

500 mg/m³ air

Basis for effect level:

other: maternal toxicity

2

Key result

Dose descriptor:

NOEC

Effect level:

50 mg/m³ air

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- Sex ratio: no differences
- Body weight gain: no differences
- External abnormalities: no treatment-related differences
- Visceral abnormalities: no treatment-related differences
- Skeletal abnormalities: reduced ossification of the 13th rib and bent ribs at the high dose group
without clear evidence of a dose-response (not significant)

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEC

Effect level:

1 000 mg/m³ air

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The following information is taken into account for any hazard / risk assessment:
In the offspring of rats exposed at up to 1000 mg/m³ during gestation days 6-15, no adverse developmental or teratogenic effects were observed after intrauterine exposure to isopropylamine.
Value used for CSA (route: inhalation):
No adverse effect observed NOAEC: 1000 mg/m³ (subacute; rat)

Executive summary:

In a study conducted in a manner quivalent or similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study), groups of 25 female Sprague-Dawley rats were exposed by whole body vapor inhalation to isopropylamine at 50, 500 or 1000 mg/m³on gestation days 6-15 (Kier and Thake, 1988). Embryonal and fetal development was not impaired following inhalation exposure of pregnant rats to high levels of isopropylamine. Maternal toxicity was observed at 1000 mg/m³, based on effects on bodyweight, treatment-related clinical signs (nasal discharge, rales, labored breathing, sneezing and fur staining/encrustation) and macroscopically observed reduced abdominal fat. The NOAEC (maternal) was 500 mg/m³, and the NOAEC (offspring) was 1000 mg/m^3.