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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexanoic acid
EC Number:
205-743-6
EC Name:
2-ethylhexanoic acid
Cas Number:
149-57-5
Molecular formula:
C8H16O2
IUPAC Name:
2-ethylhexanoic acid
Test material form:
liquid
Specific details on test material used for the study:
Purity 99.5% (Merck)

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: drinking water
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Day 6-19 of gestation
Frequency of treatment:
Daily via drinking water
Duration of test:
20 days to necropsy
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20-21 pregnant Females
Control animals:
yes, concurrent no treatment

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: Maternal toxicity - decreased body weight (10%) and water consumption (20%)

Results (fetuses)

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
skeletal malformations

Fetal abnormalities

Key result
Abnormalities:
effects observed, treatment-related
Localisation:
skeletal: forelimb
skeletal: hindlimb

Overall developmental toxicity

Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
100 mg/kg bw/day (nominal)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects occurring together with maternal toxicity effects, but not as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
Results of this study indicate that 2-EHA is teratogenic, showing a dose-dependent increase in the frequency of skeletal malformations starting at a dose level of 100 mg/kg
Executive summary:

The results indicate that 2-EHA is teratogenic, i.e., increases malformations in Wistar rats at doses which are apparently not maternally toxic, embryotoxic, or fetotoxic. There was a dose-dependent increase in the frequency of skeletal malformations starting at a dose level of 100 mg/kg. 300 mg/kg was slightly fetotoxic in females as indicated by the reduced body weight in female fetuses.

2-EHA affected particularly skeletal development of the fetuses. The spectrum of changes ranged from skeletal variants to clubfoot, including a few cases of retarded lumbar and ulna ossification.

At doses of 100 mg/kg and above, 2-EHA caused dose-dependent skeletal malformations (clubfoot, absence of fibula, polydactyly), while the development of visceral tissues was less affected.

These results indicate that 2-EHA is teratogenic in rats already at doses which are not yet maternally toxic. The skeleton appears to be the main target of 2-EHA in developing rats