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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:
1986-19-05 to 1988-29-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline 414.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

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)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Dec-1-ene, homopolymer, hydrogenated Dec-1-ene, oligomers, hydrogenated
EC Number:
500-183-1
EC Name:
Dec-1-ene, homopolymer, hydrogenated Dec-1-ene, oligomers, hydrogenated
Cas Number:
68037-01-4
IUPAC Name:
68037-01-4
Constituent 2
Reference substance name:
1-decene homopolymer, hydrogenated
IUPAC Name:
1-decene homopolymer, hydrogenated
Details on test material:
- Name of test material (as cited in study report): Stock 509
- Stability under test conditions: believed to be stable for 5 years when stored at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: approximately 8 weeks old
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: dorsal skin
- Type of wrap if used: left uncovered
- Time intervals for shavings: clipped on gestation day 0 and once weekly thereafter


TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0, 800, 2000mg/kg body weight



USE OF RESTRAINERS FOR PREVENTING INGESTION: yes cardboard Elizabethan-style collars
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: [cohoused]
- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: until showed evidence of breeding activity
- Proof of pregnancy: vaginal plug and sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
gestation days 0-19
Frequency of treatment:
once daily
Duration of test:
20 days after confirmation of impregnation (GD=20)
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 800, 2000 mg/kg
Basis:
other: applied dermally
No. of animals per sex per dose:
15 females/dose group
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: based on data obtained in a thirteen week study

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes / No / No data
- Time schedule: daily.


DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:


BODY WEIGHT: Yes
- Time schedule for examinations: 0, 3, 6, 10, 13, 16, and 20 of gestation


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: gross examination of all organs


OTHER: food consumption for gestation day intervals 0-3, 3-6, 6-10, 10-13, 13-16, and 16-20; clinical chemistry,
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: number of live and dead fetuses
Fetal examinations:
- External examinations: Yes: [all per litter ]
- Soft tissue examinations: Yes: [half per litter ]
- Skeletal examinations: Yes: [half per litter ]
Statistics:
Maternal biophase and cesarean section data, and fetal data were evaluated statistically by analysis of variance followed by group comparisons using Fisher’s Exact or Dunnett’s Test. Fetal skeletal and visceral data were recorded by hand and subsequently by ANOVA followed by group comparisons using Fisher’s Exact Test. Statistical analyses of clinical chemistry data were performed separately on individual serum components using SAS procedures. First the F-test was employed to do an analysis of variance on the serum data obtained from control and exposed groups. Next, the student-Newman-Keul’s multiple comparison test was used to identify the specific group subsets within the serum data tests identified as having nonrandom variance. In general, differences were considered statistically significant if the probability of the difference being due to chance was less than 5%.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 2 000 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Effect level:
> 2 000 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Alopecia was observed in 1 control animal and 1 animal exposed to Stock 509.  Hyperactivity was observed in 1 control animal.  Signs of dermal irritation including erythema and flaking of the skin were observed in both of the Stock 509-exposed groups.  In general, the irritation was very mild.  The mean body weight from all of the groups increased throughout the study, exhibiting normal weight gain.  Although animals from the 2000mg/kg/day group gained significantly (p<=0.5) less weight during gestation interval 13-16, the net body weight gained throughout gestation was comparable to the control group.  Mean amounts of food consumed during gestation were similar.

At the time of necropsy no findings attributable to exposure to the test material were observed.  An increase in pre-implantation loss was observed for the high-dose group due the increased preimplantation loss of three dams (29%, 53%, 27%).  However, this effect was determined to be unrelated to treatment because the number of implantation sites was not affected.

Three fetuses from one dam exposed to 800mg/kg had tails that were reduced in length.  Due to its low incidence of occurrence and an absence of dose response, this finding was concluded to be unrelated to treatment. 

Applicant's summary and conclusion

Conclusions:
The maternal NOAEL and developmental NOAEL for Stock 509 were 2000mg/kg . These findings do not warrant classification of Stock 509 as a developmental hazard under EU GHS guidelines and do not warrant classification under the EU requirements for dangerous substances and preparations.
Executive summary:

Stock 509 was administered once daily on gestation days 0-19 via dermal application to pregnant rats at doses of 0, 800, and 2000 mg/kg/day (15 rats/dose) to assess for developmental toxicity.  The rats were fitted with Elizabethan-style collars to minimize ingestion of the test material, which was applied neat and left uncovered on the skin.  Administration of Stock 509 to the skin of rats produced mild skin irritation (erythema and flaking) at the site of application. Maternal parameters (food consumption, body weight gain) monitored throughout gestation and at study termination (clinical chemistry, grossly visible abnormalities) were not adversely affected by treatment.  Reproductive parameters (number of implants, resorptions, or viable fetuses) were not adversely affected by administration of Stock 509 at any of the dose levels tested.  No evidence of abnormal development was observed during external, skeletal, or visceral examinations of fetuses from pregnant dams exposed to Stock 509.  Mean fetal body weights and crown-rump distances were similar in all of the experimental groups.  Thus, Stock 509 did not produce any maternal toxicity, fetal toxicity, or developmental effects in rats.  Based on the study results, the maternal NOAEL was 2000mg/kg/day and the developmental NOAEL was 2000mg/kg.  These findings do not warrant classification of Stock 509 as a developmental hazard under EU GHS guidelines and do not warrant classification under the EU requirements for dangerous substances and preparations.

Detailed substance identity details supporting the use of 1-decene homopolymer, hydrogenated (CAS No. 68037-01-4) as read-across can be found in ‘Section 13-Assessment Reports’ of the IUCLID dossier.