Butanone

Toxicity to reproduction

Administrative data

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Data source

Reference

Reference Type:

secondary source

Title:

No information

Bibliographic source:

ECHA database; http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d91195a-65f3-618d-e044-00144f67d249/DISS-9d91195a-65f3-618d-e044-00144f67d249_DISS-9d91195a-65f3-618d-e044-00144f67d249.html

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Deviations:

yes

Remarks:

F2 pups were not necropsied

Principles of method if other than guideline:

The P animals were re-mated and F1b fetuses were produced and examined in a teratology study.
F1a pups were reared and mated and then necropsied as adults.
F1b fetuses were necropsied for a complete teratological examination.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

Material was stated to be secondary butanol

Test animals

Species:

rat

Administration / exposure

Route of administration:

oral: drinking water

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
controls
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
3000 mg/l
Basis:
nominal in water
538 - 594 mg/kg/day

Doses / concentrations 3

Remarks:

Doses / Concentrations:
10000 mg/l
Basis:
nominal in water
1644 - 1771 mg/kg/day

Doses / concentrations 4

Remarks:

Doses / Concentrations:
20000 mg/l (F1 and F2 generations only)
Basis:
nominal in water
approx. 3000 mg/kg/day

Doses / concentrations 5

Remarks:

Doses / Concentrations:
30000 mg/l (P generation only )
Basis:
nominal in water
5089 - 4571 mg/kg/day

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Body weight gain was depressed at 30000 mg/l.

Fertility rate for the P animals treated with 30000 mg/l was 73% (below historical norms for the rat colony).
In the 20000 mg/l dose group no effect on fertility was observed in the F1 matings.

Males had slightly elevated liver and kidney weights, and females had elevated liver weights at 20000 mg/l (not statistically significant).


Compared to water, 20000 mg/l evoked changes in kidneys of rats (males more than females) including an accelerated
appearance of tubular casts and focal tubular regeneration, development of microcysts in the apices of renal papillae, and
possibly epithelial degeneration in tubules in the outer medullary zone (results of examinations mature F1).

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

10 000 mg/L drinking water

Sex:

male/female

Basis for effect level:

other: 1644 and 1771 mg/kg/day for males and females, respectively. Increased kidney weight and incidence of renal histopathological lesions at higher dose

Results: F1 generation

Details on results (F1)

Significant reduction in pup viability at birth, a reduced birthweight, and reduced survival to day 21 was seen at 30000 mg/l in the F1 generation. No treatment-related effects were seen on corpora lutea or resorptions.

No skeletal or soft tissue abnormalities or terata were observed with treatment.
Reduced birthweight was seen in the F2 pups exposed to 20000 mg/l.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

10 000 mg/L drinking water

Sex:

male/female

Basis for effect level:

other: 1644 and 1771 mg/kg/day for males and females, respectively. Decreased offspring weights ath higher dose.

Overall reproductive toxicity

Reproductive effects observed:

not specified