Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
extended one-generation reproductive toxicity - with F2 generation and developmental neurotoxicity (Cohorts 1A, 1B with extension, 2A and 2B)
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS - OECD TG 443 – Extended One Generation Reproductive Toxicity Study

NON-CONFIDENTIAL NAME OF SUBSTANCE: Benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate,

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: There are no Guideline OECD 443 or 416 studies available on S278 to evaluate the reproductive toxicity endpoint. There is a OECD 408 subchronic toxicity study available, but, based on ECHA REACH guidance on the Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance (Version 6, July 2017), these are not considered a reliable basis for prediction of reproductive hazard. The extended one-generation reproductive toxicity study (EU B.56; OECD 443) is a standard information requirement at REACH Annex X level.
- Available non-GLP studies: There are no non-GLP studies available for S278 to evaluate the reproductive toxicity endpoint.
- Historical human data: No human data exist for S278 to evaluate reproductive toxicity hazard.
- (Q)SAR: There are no recognised (Q)SAR methods available for reliable prediction of reproductive toxicity.
- In vitro methods: There are no recognised in-vitro methods available for reliable prediction of reproductive toxicity.
- Weight of evidence: There are insufficient data available currently to develop a robust weight of evidence approach.
- Grouping and read-across: This test proposal is part of a considered testing strategy to develop data on sufficient key substances to justify grouping and read-across.
- Substance-tailored exposure driven testing: Insufficient data available.
- Approaches in addition to above: None applicable.
- Other reasons: None identified.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Although weight of evidence analysis of existing data does not indicate the potential for adverse reproductive and developmental effects of S278, several data gaps have been identified for which this testing proposal is intended to cover.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- None applicable.

Data source

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Qualifier:
according to guideline
Guideline:
EU Method B.56 (Extended One-Generation Reproductive Toxicity Study)
GLP compliance:
yes
Limit test:
no
Justification for study design:
SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS:

- Premating exposure duration for parental (P0) animals - The premating exposure period will be 10 weeks, in accordance with existing ECHA guidance.
- Basis for dose level selection - Dose levels will be selected based on evaluation of the existing OECD 408 sub-chronic toxicity data available on S278 subject to a maximum dose of 1000 mg/kg/day.
- Inclusion/exclusion of extension of Cohort 1B - The proposed study design will follow the study design outlined in EU method B.56/OECD 443 - cohorts 1A and 1B with extension to include the F2 generation.
- Termination time for F2 - F2 generation will be included.
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B - Cohorts 2A and 2B will be included.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3 - Cohort 3 will not be included.
- Route of administration - oral (gavage)
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals [if applicable] - the testing will be performed on rat. The strain of rat and the vehicle will be evaluated based on the existing sub-chronic and other repeat dose toxicity data available for the substances.

It is proposed that the study will be carried out in rats using oral (gavage) administration and will follow the study design outlined in EU method B.56/OECD 443 - cohorts 1A and 1B with extension to include the F2 generation and cohorts 2A and 2B (developmental neurotoxicity). .

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzyl 3-isobutyryloxy-1-isopropyl-2,2-dimethylpropyl phthalate
EC Number:
240-920-1
EC Name:
Benzyl 3-isobutyryloxy-1-isopropyl-2,2-dimethylpropyl phthalate
Cas Number:
16883-83-3
Molecular formula:
C27H34O6
IUPAC Name:
Benzyl 2,2,4-trimethyl-1-[(2-methylpropanoyl)oxy]pentan-3-yl benzene-1,2-dicarboxylate
Constituent 2
Reference substance name:
Reaction mass of benzyl 1-(isobutyryloxy)-2,2,4-trimethylpentan-3-yl phthalate and benzyl 3-(isobutyryloxy)-2,2,4-trimethylpentyl phthalate
EC Number:
701-008-3
Molecular formula:
C27H34O6
IUPAC Name:
Reaction mass of benzyl 1-(isobutyryloxy)-2,2,4-trimethylpentan-3-yl phthalate and benzyl 3-(isobutyryloxy)-2,2,4-trimethylpentyl phthalate
Details on test material:
Identification: Santicizer® 278
Batch Number: 130521
Purity: 98%
CAS no.: 16883-83-3
Arrival Date: 4 November 2013
Production Date: 28 October 2013
Expiry / Retest Date: 10 years after the manufacturing date
Storage Conditions: (provided by the Sponsor)
At room temperature (20 ± 5 ºC), protected from humidity and in the dark
Safety Precautions: Routine hygienic procedures (gloves, goggles, face mask)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
Chemical name: benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate
CAS number: 16883-83-3
EC number: 701-008-3

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Not specified
Details on mating procedure:
Not specified
Details on analytical verification of doses or concentrations:
Not specified
Duration of treatment / exposure:
Not specified
Frequency of treatment:
Not specified
Details on study schedule:
Not specified
No. of animals per sex per dose:
Not specified

Results and discussion

Applicant's summary and conclusion

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