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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read across approach adequate to support 7.8.2 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Read across approach adequate to support 7.8.2 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
between day 6 and 15 of gestation
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
50 mg/kg bw/day
Dose / conc.:
200 mg/kg diet
Dose / conc.:
500 mg/kg bw/day
Dose / conc.:
800 mg/kg bw/day
Dose / conc.:
1 200 mg/kg bw/day
Control animals:
yes
Details on study design:
The rats were killed on day 20 and the uteri examined for number of implantation sites and for live and dead implantations.
Mortality:
mortality observed, treatment-related
Description (incidence):
Rats receiving 500 mg/kg bw or higher doses either died or were in a moribund condition and were killed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Maternal body weight gain was reduced in the 200-mg/kg bw group,
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Dose descriptor:
NOEL
Effect level:
1 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no effects
Developmental effects observed:
no

none of the gestational parameters in the

treated groups was significantly different from those of the controls. No fetal abnormalities at the max. tested concentration.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Constituent 1
Reference substance name:
Reference substance 003
Cas Number:
68603-42-9

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
20 days
Frequency of treatment:
days from 6 to 15 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw (total dose)
Dose / conc.:
100 mg/kg bw (total dose)
Dose / conc.:
300 mg/kg bw (total dose)
Dose / conc.:
1 000 mg/kg bw (total dose)
Control animals:
yes
Details on study design:
25 Controls were dosed with arachis oil. The dams were killed on day 20 of gestation

Examinations

Maternal examinations:
no death in the group

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Salivation and propulsion of the head was observed in all test groups; salivation was “severe” in the 1000 mg/kg group

Maternal developmental toxicity

Description (incidence and severity):
Post-implantation loss and total embryonic deaths were statistically significantly increased in all treated groups compared to the controls; these findings were considered incidental by the researcher because one single female accounted for these findings in each group

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: no effects

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Retardation of ossification was statistically significantly increased in the 300 and 1000 mg/kg groups; again, the researcher found this effect to be incidental because the values were within the normal range of variation for this strain. The incidence of ossification of the skull bones was statistically significantly increased in the 1000 mg/kg group; two dams accounted for 10 of the 17 findings in this group.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: no effects

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion