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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 February 2015 - 26 March 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD 414 Guideline and GLP conditions. Fully adequate for assessment.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries Testing guidelines for Toxicology studies, 12 NohSan No 8147, (24 November 2000)
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008 of 30 May 2008 test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Clear colorless liquid
Details on test material:
- Test Material: Octadecene
- CAS Number: CAS 27070-58-2
- Physical State/Appearance : Clear colorless liquid
- Molecular Formula: C18 Isomerized Olefin
- Purity: 94.1%
- Batch Number: 747273
- Label: C18 Isomerised Olefin Lot 747273
- Date Received: 3 March 2014
- Storage Conditions: Room temperature, in the dark and under nitrogen (after opening the container)
- Expiry Date: 10 February 2016

Specific details on test material used for the study:
- Test Material: Octadecene
- CAS Number: CAS 27070-58-2
- Physical State/Appearance : Clear colorless liquid
- Molecular Formula: C18 Isomerized Olefin
- Purity: 94.1%
- Batch Number: 747273
- Label: C18 Isomerised Olefin Lot 747273
- Date Received: 3 March 2014
- Storage Conditions: Room temperature, in the dark and under nitrogen (after opening the container)
- Expiry Date: 10 February 2016

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl:CD (SD) IGS BR strain
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Age at study initiation: not specified
- Weight at study initiation: 180 to 284g.
- Housing: solid-floor polypropylene cages with stainless steel mesh lids furnished with softwood flakes
- Diet (e.g. ad libitum): A pelleted diet (Rodent 2018C Teklad Global Certified Diet, Harlan UK, Oxon, UK) - free access
- Water (e.g. ad libitum): freely available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 50 ± 20%
- Air changes (per hr): 15 air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark

Experimental Starting Date: 11 February 2015
Experimental Completion Date: 26 March 2015

Justification for specie selection: the selected species is a readily available rodent species historically used in safety evaluation studies and is acceptable to appropriate regulatory authorities.


IN-LIFE DATES: From 11 February 2015 to 26 March 2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): Formulations were prepared once.
- Mixing appropriate amounts with (Type of food): The appropriate concentrations were prepared in Arachis oil solutions.
- Storage temperature of food: Stored at approximately +4 °C in the dark.

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The stability and homogeneity of the test item formulations were previously determined by Harlan Laboratories Ltd., Shardlow, UK Analytical Services (Project Number 41301656 - Octadecene CAS 27070-58-2: Ninety Day Repeated Dose Oral (Gavage) Toxicity Study in Rats). The results indicate that the prepared formulations were within 90-103% of the nominal concentration confirming the accuracy of the formulation procedure.
Details on mating procedure:
Female animals were delivered in two batches prior to Day 3 of gestation. The day that positive evidence of mating was observed was designated Day 0 of gestation.
Duration of treatment / exposure:
From Day 5 to Day 19 of gestation, by gavage
Frequency of treatment:
Daily
Duration of test:
From Day 5 to Day 19 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
24 Females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Dose levels were selected based on available toxicity data including a dose range finding study (Harlan Laboratories Ltd report number 41403655)

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS:
Once daily during the gestation period. During the dosing period, observations were recorded immediately before and soon after dosing and one hour post dosing.

BODY WEIGHT:
Individual body weights were recorded on Day 3 (prior to dosing) and on Days 5, 6, 7, 8, 11, 14 and 17 of gestation of gestation, including for surviving animals at terminal kill (Day 20).

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
Food consumption was recorded for each surviving individual animal at Day 3, 5, 8, 11, 14, 17 and 20 of gestation.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):
Daily by visual inspection of the water bottles for any overt changes.

POST-MORTEM EXAMINATIONS: Yes
- Full external and internal examination ( any macroscopic abnormalities were recorded).

Ovaries and uterine content:
Ovaries and uteri examinations:
i) Number of corpora lutea
ii) Number, position and type of intrauterine implantation
iii) Fetal sex
iv) External fetal appearance
v) Fetal weight
vi) Placental weight
vii) Gravid uterus weight
Fetal examinations:
- Fetal external findings
- Visceral findings
- Skeletal findings and skeletal development

- Number of implantations
- Embryofetal survival
- Litter size
- Sex ratio
- Mean fetal litter and placental weights


Statistics:
- Shapiro Wilk normality test and Bartlett’s test for homogeneity of variance
- Dunnett’s test
- Kruskal-Wallis nonparametric analysis of variance
- Mann-Whitney ‘U’ test
Indices:
Percentage pre-implantation loss
Percentage post-implantation loss
Sex ratio

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Mortality:
no mortality observed

Maternal developmental toxicity

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

Details on maternal toxic effects:
No maternal toxicity

Effect levels (maternal animals)

Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
no effects observed
Other effects:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No embryotoxic/teratogenic effects

Effect levels (fetuses)

Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: Developmental Toxicity

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
Based on the result of the study, the ‘No Observed Effect Level' (NOEL) for the pregnant female and the ‘No Observed Effect Level' (NOEL) for developmental toxicity is considered to be 1000 mg/kg bw/day.
Executive summary:

The test material Octadecene CAS no. 27070 -58 -2 was administrated to female pregnant rats from Day 5 to day 19 of gestation by gavage at dose levels of 100, 300 and 1000 mg/kg/day. The results did not show any maternal or foetal adverse effects.

Based on the result of this study, the ‘No Observed Effect Level' (NOEL) for the pregnant female and the ‘No Observed Effect Level' (NOEL) for developmental toxicity are considered to be 1000 mg/kg bw/day.