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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. The study is a read across from decan-1-ol (CAS 112-30-1).

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Developmental toxicology assessment of 1-octanol, 1-nonanol, and 1-decanol administered by inhalation to rats
Author:
Nelson B K, Brightwell W S, Khan A, Krieg Jr E and Hoberman A M
Year:
1990
Bibliographic source:
J. Am. Coll. Toxicol. 9:93-97 (also cited in HSDB and RTECS)
Reference Type:
review article or handbook
Title:
Developmental toxicology of industrial alcohols: A summary of 13 alcohols administered by inhalation to rats
Author:
Nelson B K, Brightwell W S, Kreig E F
Year:
1996
Bibliographic source:
Tox. Ind. Hlth. 6(3/4): 373-387

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Developmental toxicity assessment of 1-decanol administered to rats by inhalation
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-decanol
- Substance type: liquid
- Physical state: vapour
- Analytical purity: not specified but test substance was ¿reagent grade¿
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: A15B
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
- Other: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 281 g (mean)
- Fasting period before study: no data
- Housing: shoebox cages with clean heat-treated sawdust bedding for one day following impregnation, and thereafter stainless steel wire mesh cages within the inhalation exposure chambers
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 0.5 m3 Hinners-type chambers
- Method of holding animals in test chamber: animal cages were placed within the exposure chambers
- Source and rate of air: no data
- Method of conditioning air: a constant flow of decanol was mixed with a known volume of heated compressed air, resulting in vaporization of the alcohol. This was introduced into the chamber airflow system upstream from the orifice plate. The resulting turbulence downstream from the orifice plate produced a uniform mixing of the test chemical throughout the exposure chamber.
- System of generating vapour: equipment housed above exposure chambers in sealed glove boxes maintained under negative pressure to prevent vapour leakage
- Temperature, humidity, pressure in air chamber: temperature 26±0.6 deg C (mean ± SD) and relative humidity 37±4% (from hourly measurements during exposure).
- Air flow rate: 0.5 m3/min (dynamic)
- Air change rate: no data
- Method of particle size determination: no data
- Treatment of exhaust air: no data

TEST ATMOSPHERE
- Brief description of analytical method used: Continuous recording by a Miran 1A general purpose infrared analyzer and confirmatory analysis twice per week with charcoal tube samples analyzed using gas chromatography.
- Samples taken from breathing zone: yes

VEHICLE (if applicable)
Heated compressed air

Other: Calibration checks of analyzer were conducted daily. 87% were within 5% of the target concentrations; all were within 10%.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Test substance concentration within the exposure chamber was measured hourly during exposure days by a Miran 1A general purpose infrared analyzer calibrated within ±50% of the target concentration (2 data points above and two data points below, evenly spaced, with a minimum of 3 samples per data point). Confirmatory analysis twice per week with charcoal tube samples analyzed using gas chromatography.
Details on mating procedure:
- Impregnation procedure: presumably cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: no data
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear
- Any other deviations from standard protocol: no data
Duration of treatment / exposure:
19 days
Frequency of treatment:
6 hours/day
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/m3
Basis:
other: nominal target concentration, confirmed by analytical analysis
No. of animals per sex per dose:
~15 females
Control animals:
yes, historical
Details on study design:
- Dose selection rationale: the highest concentration which could be generated as a vapour at room temperature.
- Rationale for animal assignment (if not random): Females were assigned without bias to groups as they became pregnant to make efficient use of the inhalation chambers.
- Other:
- Control animals: composite control group consisted of 11 control groups used by the same authors in previous studies of 13 alcohols over 5 years.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: daily during the first week of exposure and weekly thereafter

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus, ovaries

OTHER: Total feed and water intake were measured at weekly intervals on days 7, 14 and 20 of pregnancy.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Other: live foetuses counted
Fetal examinations:
- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter]
- Head examinations: No
Statistics:
- One-way multivariate analysis of variance (MANOVA) and possibly analysis of variance (ANOVA) used for corpora lutea, number of resorptions, sex ratio, pup weight (a significant MANOVA indicated an ANOVA analysis).
- ANOVA analysis for maternal weights, feed and water intake; Greenhouse-Geisser estimate of epsilon was used for these (to adjust the degrees of freedom of the within-litter main effects and interaction).
- Variance Test for Homogeneity of the Binomial Distribution or an ANOVA was used for analysis of foetal ¿incidence¿ data; the Kruskal-Wallis test was used if a non-parametric analysis was ¿more appropriate¿.
Indices:
no data
Historical control data:
no concurrent controls, only historical controls

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No statistically significant treatment-related adverse effects on maternal weight gain, feed consumption, water intake, mean corpora lutea/litter, or mean resorptions/litter in dams exposed to air containing 0.1 mg decanol/L from GD 1-19, compared to controls.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEC
Effect level:
> 100 mg/L air (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
> 100 mg/L air (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No statistically significant treatment-related adverse effects were observed on litter size and weights, sex ratio, grossly visible abnormalities, or external, soft tissue and skeletal abnormalities (data not presented), compared to controls.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Composite control data for this test substance were not presented. Said to be available ¿from the authors¿; the majority are published in Nelson BK et al. (1990). Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats. Tox. Ind. Hlth V6, reported as ¿in press¿.

 

Mean vapour concentrations were 100±3 mg/m3as measured by the infrared analyzer. The concentration calculated using the charcoal tubes (57±7 mg/m3) was deemed to be unreliable, possibly due to absorption of 1-decanol onto the glass wool in front of the charcoal in the sampling tubes.


ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: Within 5
-10% of the nominal  concentration of 0.1 mg/l when measured by Infrared analysis. This is the  highest attainable dose under the conditions of the study. Actual dose achieved 0.1 mg/l.

MATERNAL TOXIC EFFECTS BY DOSE LEVEL: 
- Mortality and day of death: None
- Number pregnant per dose level: Not reported
- Number aborting: Not reported
- Number of resorptions: Comparable in treated and control groups. Mean resorptions/litter control 0.5, treated 0.5.
- Number of corpora lutea: Comparable between treated and control groups. Mean corpora lutea/litter control 14.9, treated 13.8.
- Duration of Pregnancy: Not reported.
- Body weight: Weight gain was comparable in treated and control groups.
- Food/water consumption: Comparable between treated and control groups.
- Description, severity, time of onset and duration of clinical signs:  None
- Hematological findings incidence and severity: Not carried out.
- Clinical biochemistry findings incidence and severity: Not carried out.
- Gross pathology incidence and severity: Not carried out.
- Organ weight changes: Not carried out.
- Histopathology incidence and severity: Not carried out.

FETAL DATA: 
- Litter size and weights: Comparable between treated & control groups.  Litter size (mean) control 13.5, treated 13,1.
- Sex ratio: No significant difference between treated and controls.  Controls/litter (mean) male 6.6, female 6.9; Treated/litter (mean) male  6.8, female 6.3.
- External, Soft tissue and Skeletal abnormalities: No treatment related effects.

Applicant's summary and conclusion

Conclusions:
In a reliable study, the NOAEC for maternal toxicity, foetotoxicity and teratogenicity to rats following inhalation exposure to n-decanol from gestationdays 1-19 was 0.1 mg/l (the highest attainable concentration at room temperature).