Cyclododeca-1,5,9-triene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference 1

Title:

No information

Author:

DuPont Co. (1999). Haskell Laboratory Report No. DuPont-1559 (unpublished);|cited in DuPont Co. (2001). Robust summary for 1,5,9-cyclododecatriene. Submitted to U.S. EPA on 11 Dec. 2001. Also cited in TSCA fiche OTS0557883-1

Reference 2

Reference Type:

publication

Title:

Evaluation of the potential developental toxicity of cyclodedecatriene (CDDT).

Author:

Munley SM, Kelly DP and Kennedy GL jr.

Year:

2003

Bibliographic source:

Drug Chem. Toxicol. 26 (3), 199-212.

Reference 3

Reference Type:

publication

Title:

Robust summary for 1,5,9-cyclododecatriene (revised).

Author:

DuPont Safety, Health & Environmental Excellence Center, Wilmington (Del., USA)

Year:

2003

Bibliographic source:

U.S. EPA, 46 pp

Materials and methods

Principles of method if other than guideline:

Method: details see reference

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,5,9-cyclododecatriene

IUPAC Name:

1,5,9-cyclododecatriene

Constituent 2

Reference substance name:

Cyclododeca-1,5,9-triene

EC Number:

225-533-8

EC Name:

Cyclododeca-1,5,9-triene

Cas Number:

4904-61-4

Molecular formula:

C12H18

IUPAC Name:

cyclododeca-1,5,9-triene

Details on test material:

1,5,9-cyclododecatriene of DuPont Nylon, purity 99.83%

Test animals

Species:

rat

Strain:

other: Crl:CD (SD)BR

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Source: Charles River Breeding Laboratories, Raleigh (North Carolina,  USA)
- females; age: 51-70 days when received (at 1, 2, or 3 days of gestation); 5, 4,  or 3 days acclimation
- Number of animals: 22 per exposure concentration

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Details on exposure:

ADMINISTRATION / EXPOSURE
- Type of exposure: whole-body
- Concentrations: 10 / 25 / 75 ppm (target)
- Type or preparation of particles: Controlled flows of high-pressure air  and liquid test substance through heated mixing flask (approx. 240 °C),  dilution with additional air, total airflow 60 l/min (target; measured:  59 - 62 l/min).
- Exposure chamber temperature: target 22 +/- 2 °C; measured 22 - 27 °C

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Concentration monitoring:   known volume samples from breathing zone at 60 minute intervals;   passage through glass fiber filter followed by glass impinger with  hexane as collection medium;   weighing of filter before and after sampling;   GC / FID analysis of hexane solution, quantification with standard  curve.
- Particle size (high test concentration, 3 measurements): MMAD 5.4 / 1.5  / 0.76 µm, mean 2.6 µm, with 13-56% of the particles < 1 µm; 35-89% < 3  µm; 66-99% < 10 µm.
-further details: see references

Details on mating procedure:

-mated by supplier

Duration of treatment / exposure:

days 6-20 of gestation

Frequency of treatment:

6 hours/day

Duration of test:

Duration of test: 16 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10; 25; 67 ppm = 67.5; 169; 452 mg/m3
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10 +/- 0.27 ppm; 25 +/- 0.33 ppm; 67 +/- 1.9 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

22 per exposure concentration

Control animals:

yes, concurrent vehicle

Details on study design:

Sex: female

Examinations

Maternal examinations:

PARAMETERS ASSESSED DURING STUDY:
- Body weight gain: days 0, 6, 8, 10, 12, 14, 16, 18, 20, 21
- Food consumption: days 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 21
- Clinical observations: once daily (before onset of exposure; including  day 21), on exposure days also 1 h after exposure

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): Study  terminated on day 21
- Macroscopic: Organs of the thoracic and abdominal cavities

Ovaries and uterine content:

- Examination of uterine content: type (live and dead fetuses, and  resorptions) and relative positions 

Fetal examinations:

- Examination of fetuses: body weight, sex, and external alterations;  visceral alterations and stages of renal papillary development (live  fetuses 1, 3, 5 etc. for each litter), skeletal alterations (all live  fetuses)

Statistics:

STATISTICAL METHODS: 
- Maternal weight, weight change, food consumption: parametric linear  contrast of means
- Incidence data (pregnancy, clinical observations): Cochran-Armitage test
- Reproductive outcome data and fetal alteration data: Jonckheere's test;  at > 75 % ties: permutation methodology
- Mean fetal weight, sex ratio: Analysis of variance (ANOVA), applying a  parametric linear contrast of least square means

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
MATERNAL TOXIC EFFECTS BY DOSE LEVEL:
- Mortality and day of death: no deaths
- Description, severity, time of onset and duration of clinical signs:    10 ppm: no effect; 25 ppm: increase in facial staining;   67 ppm: diminished response to alerting stimulus; stained and/or wet  fur, staining was considered to be the result of increased lacrimation  and salivation and decreased grooming.
- Body weight: statistically significant decrease at mid and high dose  beginning on day 8; data for day 21:   25 ppm:  -5.3% absolute,  -5.6% corrected for uterine content   67 ppm: -14.8% absolute, -15.0% corrected for uterine content   increase day 6-21 (also statistically significant):   25 ppm: -14.5% absolute, -30.8% corrected for uterine content   67 ppm: -36.0% absolute, -69.6% corrected for uterine content   At 10 ppm, statistically significant but minimal (3-4 %) and transient  differences to control in weight increase were observed during the first  week.
- Food/water consumption:   The maternal weight data corresponded to food consumption values, which  were reduced at 25 (-9%) and 67 (-28%) ppm but unaffected at 10 ppm.
- Number pregnant per dose level = number of litters:   0 ppm: 21;  10 ppm: 20;  25 ppm: 22;  67 ppm: 20. ==> no effect
- Number aborting: none - Number of resorptions (mean):   0 ppm: 1.0; 10 ppm: 0.7; 25 ppm: 0.4; 67 ppm: 0.7 ==> no effect
- Number of implantations (mean):   0 ppm: 14.1; 10 ppm: 14.1; 25 ppm: 13.3; 67 ppm: 13.8 ==> no effect
- Pre and post implantation loss: none - Number of corpora lutea (mean):   0 ppm: 15.6; 10 ppm: 15.4; 25 ppm: 14.8; 67 ppm: 15.0 ==> no effect

Effect levels (maternal animals)

1

Dose descriptor:

NOEL

Effect level:

10 ppm

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOEL

Effect level:

25 ppm

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
FETAL DATA: 
- Litter size and weights (mean):    0 ppm: 13.1 fetuses (6.9 males + 6.2 females) with 5.68 g mean weight   10 ppm: 13.4 fetuses (7.1 males + 6.4 females) with 5.63 g mean weight   25 ppm: 13.0 fetuses (6.6 males + 6.4 females) with 5.55 g mean weight   67 ppm: 13.1 fetuses (6.5 males + 6.7 females) with 4.93 g mean weight   ==> statistically significant effect on weight (-13.2%) at 67 ppm
- Number viable: all live
- Sex ratio: male/total = 0.53 / 0.52 / 0.50 / 0.49 ==> no effect
- Grossly visible abnormalities: no effect observed
- External abnormalities: no effect observed
- Skeletal abnormalities:    Compound related, statistically significant increase in incidence of  delayed skeletal ossification:   
- sternebrae: 0 ppm: -; 10 ppm: 1 fetus; 25 ppm: 2 fetuses (2 litters);  67 ppm: 8 fetuses (5 litters): considered compound-related and consistent  with reduced fetal weight.   
- vertebrae: 0 ppm: 113 fetuses (21 litters) 10 ppm: 123 (20); 25 ppm:  134 (22); 67 ppm: 136 (20): not considered toxicologically relevant based  on high background incidence; well within the control range of four  studies from the same time: 128-161 fetuses in 23-25 litters.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Result: no selective developmental toxicant