Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
publication
Title:
Teratogenic effects of various di-n-butyltins with different anions and butyl(3-hydroxybutyl)tin dilaurate in rats.
Author:
Noda T et al
Year:
1993
Bibliographic source:
Toxicology, 85, 149-160.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
see attached report
Principles of method if other than guideline:
The number of animals and dose groups used in this study were less than the recommended amounts in OECD Guideline 414. Study meets generally accepted scientific standards, is well documented, and acceptable for assessment.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
dibutyltin diacetate
IUPAC Name:
dibutyltin diacetate
Constituent 2
Chemical structure
Reference substance name:
Dibutyltin di(acetate)
EC Number:
213-928-8
EC Name:
Dibutyltin di(acetate)
Cas Number:
1067-33-0
Molecular formula:
C12H24O4Sn
IUPAC Name:
dibutyltin di(acetate)
Details on test material:
- Name of test material (as cited in study report): di-n-butyltin diacetate (di-n-butyltin anion, diacetate (DBTA)); Tokyo Chemical Industry Co. Ltd (Tokyo Japan)

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CLEA Japan Inc. (Tokyo Japan
- Age at study initiation: 4 weeks
- Housing: Housed individually
- Diet (e.g. ad libitum): NMF, Oriental Yeast Co., Ltd. Tokyo Japan ad libitum
- Water (e.g. ad libitum): Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2 °C
- Humidity (%): 60 ± 10%
- Photoperiod (hrs dark / hrs light): dark/light cycle (dark period from 7 pm to 7 am)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Three month old female Wistar rats were paired with single males of the same age
- Impregnation procedure: Cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: Overnight

- Verification of same strain and source of both sexes: Yes
- Proof of pregnancy: Sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
Dibutyltin diacetate (DBTA) was dissolved in olive oil and administered  via gavage to 10 pregnant rats at a single dose of 80 µmol/kg on Day 8 of gestation.
Frequency of treatment:
Single oral dose.
Duration of test:
Dams were sacrificed on Day 20 of gestation. 
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
1.7 mg/kg bw/day (nominal)
Dose / conc.:
5 mg/kg bw/day (nominal)
Dose / conc.:
10 mg/kg bw/day (nominal)
Dose / conc.:
15 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10 females
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
vaginal bleeding and piloerection in 15 mg/kg bw day group
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
effects observed, treatment-related
Description (incidence and severity):
dose dependend thymus athrophie in all exposed groups
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
dose dependend thymus athrophie in all exposed groups
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
dose dependend thymus athrophie in all exposed groups
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Maternal developmental toxicity

Number of abortions:
effects observed, treatment-related
Pre- and post-implantation loss:
effects observed, treatment-related
Total litter losses by resorption:
effects observed, treatment-related
Early or late resorptions:
effects observed, treatment-related
Dead fetuses:
effects observed, treatment-related
Changes in pregnancy duration:
not examined
Changes in number of pregnant:
not examined
Other effects:
not examined

Effect levels (maternal animals)

Key result
Dose descriptor:
LOAEL
Effect level:
1.7 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
immunology
other: maternal toxicity

Maternal abnormalities

Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: thymus

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Reduction in number of live offspring:
effects observed, treatment-related
Changes in sex ratio:
effects observed, non-treatment-related
Changes in litter size and weights:
effects observed, treatment-related
Changes in postnatal survival:
not examined
External malformations:
effects observed, treatment-related
Skeletal malformations:
effects observed, non-treatment-related
Visceral malformations:
effects observed, non-treatment-related
Other effects:
not examined
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
external malformations

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
10 mg/kg bw/day (nominal)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects 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:
Dibutyltin diacatate causes maternal toxicity at levels of 1-.7 mg/kg/bw day. Developmental effects are observed at 10 mg/kg bw day
Executive summary:

In the oral (gavage) teratogenicity study in the rat the test material was determined, not to be toxic maternally, but was teratogenic to developing fetuses.

The predominant external malformation of foetuses exposed to DBTA on gestation day were mandible complications suchs as cleft mandible, cleft lower lip, ankyloglossia and schistoglossia. Skeletal malformations such as anomaly of mandibular fixation, cranial hypoplasia and fused ribs etc were also observed.