2-[(1-methylpropyl)amino]ethanol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Materials and methods

Principles of method if other than guideline:

N-Methylethanolamine was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylaminoethanol

EC Number:

203-710-0

EC Name:

2-methylaminoethanol

Cas Number:

109-83-1

IUPAC Name:

2-(methylamino)ethanol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-methylaminoethanol
- Analytical purity: no data
- Lot/batch No.: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study:
- Housing: alone in 38 x 33 x 17-cm polycarbonate cages with filter tops
- Diet: Purina Lab Chow ad libitum
- Water: tap water ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +/- 2
- Humidity (%): 40 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Vehicle:

clean air

Details on exposure:

Pregnant females were transported from the animal quarters to the inhalation chambers in their home cages with filter tops (Hazleton Systems, Aberdeen, MD). They were placed individually in 13 x 25 x 189-cm stainless steel wire mesh cages within exposure chambers.
Air flow through the chambers provided approximately four air changes per minute.
Exposures were conducted sequentially in one or two chambers, with a third chamber for sham exposure of control subjects.
Control animals were placed in similar chambers for the same hours as the exposed animals; a pooled group of controls (N = 34) served as the comparison group for the first three chemicals examined. Another group of 15 controls served as the comparison group for the last two chemicals examined, as these groups were exposed at a later time (approximately 6 months later) than the first three.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The concentrations within the exposure chambers as measured by the infrared analyzer were relatively close to those obtained from gas chromatography.

Details on mating procedure:

Males weighing over 300 g were placed individually into a cage with three females weighing 200 to 300 g. Vaginal smears were taken each morning, and the presence of sperm marked day zero of gestation.

Duration of treatment / exposure:

Exposures conducted 7 hr/day, and the animals were left in the chamber for at least one additional hour blow-off time after vapor generation terminated. They were then returned in their individual housing cages to the animal quarters, where water bottles were replaced.

Frequency of treatment:

Exposures were conducted on gestation days 7-15.

Duration of test:

On day 20 of gestation, dams were sacrificed.

Doses / concentrations

Remarks:

Doses / Concentrations:
150.0 +/- 15.2 ppm (460 +/- 46 mg/m3)
Basis:
analytical conc.

No. of animals per sex per dose:

approximately 15 pregnant rats

Control animals:

other: three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls.

Examinations

Maternal examinations:

Feed and water intake and maternal weight were recorded weekly (i.e., on days 7, 14, and 21); any other signs of maternal toxicity were noted daily.
On day 20 of gestation, the females were individually weighed and euthanized by chloroform asphyxiation.

Ovaries and uterine content:

The entire uterus was removed and numbers of resorption sites (classified as early, middle or late) and live fetuses wvere determined.

Fetal examinations:

Fetuses were serially removed, blotted of excess fluids, weighed, examined for external malformations and external sex determined.
One third of the fetuses were randomly selected and placed in 95% ethanol, and the remainingfetuses were placed in Bouin's solution. After being in
the Bouin's solution for at least 1 week, these fetuseswere examined for visceral abnormalities using Wilson's razor blade sectioning technique. The viscera wereexamined with the aid of a dissecting microscope. A representative sample of sections with malformations was identified by dam number and saved in 70% alcohol.

Fetuses were examined for skeletal defects by using a modified Staples technique. They were fixed in 95% alcohol, eviscerated and macerated in 2% KOH/Alizarin Red S solution. The fetuses were further macerated and cleared in the appropriate solutions of 2% KOH/glycerin (60:40, 40:60, 20:80) and stored in 100% glycerin. A crystal of thymol was added to each storage vial to retard fungal growth. Storage vials were individually identified by dam number.

Statistics:

Numbers of implants and proportions of resorptions were independently analyzed by using a Kruskal-Wallis test corrected for ties, with subsequent multiple comparisons to determine where the differences occurred. Analysis of pup weights involved a mixed model analysis of covariance (with the number of live pups in the litter as the covariate) using maximum likelihood estimation. The model was mixed, since there was both within-litter and between-litter variation. Subsequently, pairwise comparisons between the pooled control group and each treatment group were performed. Incidence oftotal defects and of total variants were compared using a Kruskal-Wallis test with multiple comparisons with the litter as the experimental unit and the level of significance at p< 0.05.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Effects upon pregnancy outcome:
Number pregnant/mated - 15/16 (Control); 18/24 (Treated)
Implants/dam - 13.1 (Control); 11.9 (Treated)
Litters with resorptions - 10 (67%; Control); 10 (56%; Treated)
Live fetuses/litter - 11.6 (Control); 11.8 (Treated)

Effect levels (maternal animals)

1

Dose descriptor:

NOAEC

Effect level:

>= 150 other: ppm (analytical) (460 mg/m3)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEC

Effect level:

>= 150 other: ppm (analytical) (460 mg/m3)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Live fetal body weights - Female, 3.36 (Control); 3.59 (Treated); Male, 3.33 (Control); 3.69 (Treated)
Number of litters with abnormal litter - 5 (Control); 7 (Treated)

Visceral observations (litters/fetuses):
Number litters/fetuses examined - 15/116 (Control); 18/143 (Treated)
Malformations - Brain (hydrocephalus, mild), 3/6 (Control); 3/5 (Treated).
Variations (62 controls; 74 treated) - Testicular (undescended testes) - 0 (Control); 1/1 (Treated); Testicular (position variation) - 10/22 (Control); 9/13 (Treated) - Urinary tract (dilated renal pelvis) - 3/ 4 (Control); 5/5 (Treated); Urinary tract (dilated ureter) - 3/6 (Control); 6/18 (Treated); Urinary tract (hydronephrosis) - 2/2 (Control); 0 (Treated); Urinary tract (hydroureter) - 3/3 (Control); 5/6 (Treated); Urinary tract (ectopic kidney) - 1/1 (Control); 0 (Treated).
% Normal (mean ±standard deviation) - 89 ±26% (Control); 92 ±15% (treated)
% Abnormal (mean ±standard deviation) - 11 ±26% (Control); 8 ±15% (treated)

Skeletal observations (litters/fetuses):
Number litters/fetuses examined - 14/58 (Control); 18/69 (Treated)
Malformations - 0 (Control); 0 (Treated)
Variations - Ribs (rudimentary 14th) - 1/1 (Control); 1/2 (Treated); Ribs (rudimentary lumbar) - 0 (Control); 1/1 (Treated); Skull (incomplete ossification of supraoccipital) - 0 (Control); 1/1 (Treated); Skull (incomplete ossification of interparietal) - 1/1 (Control); 1/2 (Treated); Skull (incomplete ossification of parietal) - 1/1 (Control); 0 (Treated); Sternebrae (decreased number) - 1/1 (Control); 1/1 (Treated); Sternebrae (split) - 0 (Control); 1/1 (Treated); Sternebrae (misaligned) - 1/1 (Control); 5/5 (Treated); Centra (misshapen thoracic) - 1/1 (Control); 5/5 (Treated); Pelvic Girdle (pubis missing) - 0 (Control); 2/2 (Treated); Pelvic Girdle (ischium missing or reduced in size) - 0 (Control); 1/1 (Treated).
% Normal (mean ±standard deviation) - 100 ±0% (Control); 100 ±0% (treated)
% Abnormal (mean ±standard deviation) - 0% (Control); 0% (treated)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

N-Methylethanolamine showed neither maternal nor fetal toxicity effects.

Executive summary:

N-Methylethanolamine was vaporized and administered at 150 ppm to approximately 15 pregnant rats for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20 of gestation. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. As overall result for the substance N-Methylethanolamine it can be stated that neither maternal nor fetal toxicity effects can be concluded in this study.