2-butoxyethanol

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1953

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Old and briefly reported study but one which meets basic scientific principles and contributes to the understanding of the influence of haemotoxicity on developmental toxicity

Data source

Reference

Reference Type:

publication

Title:

Influence of severe hemorrhagic anemia during pregnancy on development on the offspring in the rat.

Author:

Wilson JG

Year:

1953

Bibliographic source:

Proc Soc Exp Biol Med, 84, p66-69.

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Study designed to assess the influence of anaemia on pregnant rats. Anaemia induced by free bleeding.

GLP compliance:

no

Remarks:

study pre-dates GLP

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Study does not use any xenobiotic substance

IUPAC Name:

Study does not use any xenobiotic substance

Details on test material:

Study does not use any xenobiotic substance but looks at effects of anaemia on pregnancy.

Test animals

Species:

rat

Strain:

not specified

Sex:

female

Administration / exposure

Route of administration:

other: not applicable

Vehicle:

other: not applicable

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

not applicable

Frequency of treatment:

not applicable

Duration of test:

to GD 20

No. of animals per sex per dose:

25-40 per 'bleed group'

Control animals:

yes

Results and discussion

Effect levels

1

Basis for effect level:

other: Severe anaemia, with haematocrit values below 16.5 -17 (from normal values of 39 -42), increased the likelihood of maternal death significantly - an effect that was consistent whatever the treatment period

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

2

Basis for effect level:

other: Milder anaemia (haematocrit values in the low 20's) increases the likelihood of complete resorptions but only when it occurs over the period GD7 -11.

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Observed effects

See remarks below

Any other information on results incl. tables

For dams bled on gd 7- 9, removal of 5 to 5.9 cc blood per 100 g body weight resulted in a 52 % decrease in haematocrit (relative to controls) and totally resorbed litters for 33 % of pregnancies (3 of 9). Haemorrhages in excess of 6 cc caused a 63 % decrease in haematocrit and early termination of 13 out of 15 pregnancies due to either maternal death (8 dams) and total resorbed litters (5 dams). For dams bled on gd 9-11, 25 % of dams losing 5-5.9 cc per 100 g body weight exhibited a 54 % decrease in haematocrit and totally resorbed litters with 1 of 8 term litters (gd 20) exhibiting retarded development. For dams with more severe anemia (in excess of 6 cc with a 59 % decrease in hematocrit), one third exhibited total resorbed litters. Of the 13 pregnancies with fetuses surviving to term (gd 20), the mean rate of prenatal survival was decreased (18 % of fetuses resorbed). Four litters exhibited growth retardation (delay).

Bleeding the dams on the 11-13 or 13-15 days of pregnancy caused a higher rate of maternal death (45 % of dams). In some cases, death of the fetuses preceded death of the dam. Total litter loss due to resorption was not seen at these time points. Some delayed development was seen. Bleeding that was initiated on gd 9 had the greatest likelihood of resulting in malformation, growth retardation (4 of 13 litters), or increased rate of resorption.

Applicant's summary and conclusion

Conclusions:

The authors concluded that “although an occasional abnormality may be produced at this time, maternal anemia usually causes either early termination of pregnancy or permits continuation of pregnancy without detriment to the young.” The critical period for anaemia causing resorptions is GD7-11.

Executive summary:

In an old but well reported study, the effect of anaemia on pregnancy in rats was examined. Anaemia was induced by inflicting blood loss. Treatment was carried out for different 3 day periods between GD7 and 15. Severe anaemia, with haematocrit values below 16.5 -17 (from normal values of 39 -42), increased the likelihood of maternal death significantly - an effect that was consistent whatever the treatment period. Milder anaemia (haematocrit values in the low 20's) increases the likelihood of complete resorptions but only when it occurs over the period GD7 -11. There was evidence of growth retardation in a small number of litters. The authors concluded that maternal anemia usually causes either early termination of pregnancy or permits continuation of pregnancy without detriment to the young.