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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
- lack of data on test substance
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
189200-42-8
Cas Number:
189200-42-8
IUPAC Name:
189200-42-8
Details on test material:
- Name of test material: only trade name given
- Physical state: pale yellow liquid
- Analytical purity: no data
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
other: Crl:CD BR VAF/Plus

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: polyethylene glycol (PEG 400)
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
- Impregnation procedure: cohoused
- M/F ratio per cage: 1/1
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug and/or sperm in vaginal smear referred to as day 0 of pregnancy
After confirmation of pregnancy, each mated female was returned to its cage and new females were placed into the males' cages until a required number of pregnant females was obtained.
Duration of treatment / exposure:
gestation days (GD) 6 - 15
Frequency of treatment:
daily, 7 d/week
Duration of test:
21 d (GD 0 - 21)
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 500 and 1000 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
25 females per dose, 50 males in total
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Table 1: Litter data and fetal body weight

 

 

Control

dose groups [mg/kg bw/day]

 

100

500

1000

No. of dams/litters examined

25

21

23

25

Mean no. of Corpora Lutea

16.8

16.8

17.7

16.8

± 2.28

± 2.50

± 3.50

± 1.82

n=25

n=20

n=23

n=25

Mean no. of Implantation Sites

15.76

15.9

16.09

15.52

± 2.24

± 2.62

± 2.25

± 2.49

n=25

n=21

n=23

n=25

Mean no. of resorptions

0.88

0.81

0.91

0.56

± 1.05

± 1.29

± 1.12

± 0.82

n=25

n=21

n=23

n=25

Pre-implantation loss [%]

5.7

6.7

8

7.7

± 8.1

± 8.2

± 8.2

± 12.9

n=25

n=20

n=23

n=25

Post-implantation loss per litter [%]

5.4

4.9

6

4.4

± 6.4

± 7.7

± 7.3

± 6.4

n=25

n=21

n=23

n=25

Mean no. of live fetuses

14.88

15.1

15.13

14.88

± 2.19

± 2.64

± 2.46

± 2.64

n=25

n=21

n=23

n=25

Mean no. of dead fetuses

0

0

0.04

0.08

 

 

± 0.21

± 0.28

n=25

n=21

n=23

n=25

Mean no. of female fetuses

7.72

7.48

8.04

7.8

± 2.28

± 3.11

± 2.29

± 1.78

n=25

n=21

n=23

n=25

Mean no. of male fetuses

7.16

7.62

7.09

7.08

± 1.93

± 2.25

± 2.09

± 2.58

n=25

n=21

n=23

n=25

Mean body weight (female fetuses) (g)

5.04

5.05

5.06

5.2

± 0.44

± 0.32

± 0.46

± 0.37

n=188

n=157

n=185

n=195

Mean body weight (male fetuses) (g)

5.33

5.27

5.39

5.44

± 0.52

± 0.39

± 0.38

± 0.38

n=175

n=160

n=163

n=177

Table 2: Fetal variations and malformations

 

 

Control

dose groups [mg/kg bw/day]

 

100

500

1000

No. of fetuses with external variations

0

0

0

0

n=372

n=317

n=347

n=358

No. of fetuses with external malformations

0

1

3

0

n=372

n=317

n=347

n=358

No. of fetuses with visceral or head variations

0

0

1

2

n=187

n=161

n=173

n=186/187*

No. of fetuses with visceral or head malformations

2

2

1

0

n=187

n=161

n=173

n=186/187*

No. of fetuses with skeletal variations

45

39

29

35

n=185

n=156

n=176

n=185

No. of fetuses with skeletal malformations

1

3

0

2

n=185

n=156

n=176

n=185

  

*186 visceral examinations performed, 187 head examinations performed

Applicant's summary and conclusion

Conclusions:
The test substance was not considered embryotoxic under the conditions of this study. Accordingly, the maternal and developmental NOAELs were established at 1000 mg/kg bw/d under the conditions of this study. The results indicate that test substance was not a selective developmental toxicant and was not embryotoxic or teratogenic under the conditions of this study.