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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to OECD 421 dd 2 October 2013, under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Reference substance name:
624-48-5
IUPAC Name:
624-48-5
Constituent 2
Chemical structure
Reference substance name:
Dimethyl maleate
EC Number:
210-848-5
EC Name:
Dimethyl maleate
Cas Number:
624-48-6
Molecular formula:
C6H8O4
IUPAC Name:
dimethyl (Z)-but-2-enedioate
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
see 7.8.1 Toxicity to reproduction

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
see 7.8.1 Toxicity to reproduction

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
see 7.8.1 Toxicity to reproduction
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
see 7.8.1 Toxicity to reproduction
Duration of treatment / exposure:
First Test Item Adminismtration: Day 1 of pre-pairing
Pre-Pairing: 14 days
Pairing: 14 days maiximum
Gestation: Approx. 21 days
Treatment ends: females: on day 3 post partum; males: on day before sacrifice
Necropsy: females: on day 4 post partum; males: After a minimum of 28 days treatment.
Frequency of treatment:
Daily

Doses / concentrations
Remarks:
Doses / Concentrations:
Exposure groups: 0, 50, 200 and 400 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
per dose group: 12 males and 12
Control animals:
yes, concurrent vehicle
Details on study design:
see 7.8.1 Toxicity to reproduction

Examinations

Observations and examinations performed and frequency:
see 7.8.1 Toxicity to reproduction
Sacrifice and pathology:
see 7.8.1 Toxicity to reproduction
Other examinations:
see 7.8.1 Toxicity to reproduction
Statistics:
see 7.8.1 Toxicity to reproduction

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOEL (No Observed Effect Level) for general toxicity in males and females was considered to be below 50 mg/kg/day, but the NOAEL (No Observed Adverse Effect Level) for general toxicity in males and females was considered to be 200 mg/kg/day.
The NOEL (No Observed Effect Level) and the NOAEL (No Observed Adverse Effect Level) for reproduction/developmental toxicity was considered to be 200 mg/kg/day.
Executive summary:

see 7.8.1 Toxicity to reproduction

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