Registration Dossier

Diss Factsheets

Toxicological information

Toxicity to reproduction: other studies

Currently viewing:

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/report meeting basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1998
Reference Type:
secondary source
Title:
European risk assessment report, Styrene CAS No: 100-42-5 EINECS No 202-851-5, Draft for publication, June 2008 United Kingdom
Author:
European Union
Year:
2008

Materials and methods

Principles of method if other than guideline:
Low and high doses of the styrene oligomer migrates of 23 polystyrene samples [i.e. 9 general purpose polystyrenes (GPPS), 8 high impact polystyrenes (HIPS) and 6 expandable polystyrenes (EPS)] were tested for estrogenicity in an in vivo uterotrophic assay (immature females rat model). 2 concentrations of migrates of each of the 23 polystyrenes tested were selected to simulate daily human consumption of a low and high amount of food.
GLP compliance:
yes
Type of method:
in vivo

Test material

Constituent 1
Reference substance name:
Reference substance 002
Details on test material:
- Name of test material (as cited in study report): polystyrene: GPPS (general purpose polystyrenes), HIPS (high impact polystyrenes), EPS (expandable polystyrenes); PSNUMB01 to PSNUMB23
- Molecular formula (if other than submission substance): no data
- Molecular weight (if other than submission substance): 116,162 (homopolymer), according to NLM ChemIDplusAdvanced
- Analytical purity: not reported
- Impurities (identity and concentrations): EPS: n-pentane (CAS 109-66-0), iso-pentane (CAS 78-78-4); not reported for GPPS and HPS
- Storage condition of test material: room temperature (20-25°C)

Test animals

Species:
rat
Strain:
other: Wistar (Chbb:THOM-SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach/Riss, Germany
- Age at study initiation: 22 ± 1 days
- Weight at study initiation: 40-60 g
- Fasting period before study: no data
- Housing: Individually in M-II Makrolon cages (Becker & Co., Castrop-Rauxel, Germany
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 48 hours


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
ethanol
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
25% in ethanol, preparation at two-week intervals

VEHICLE
- Justification for use and choice of vehicle (if other than water): preliminary studies were performed at the BASF Department of Toxicology to identify a non-toxic vehicle and dose-volume. Acceptable vehicle and dose volume was identified as 25 % ethanol administered twice daily at dose volumes of 10 ml/kg.
- Concentration in vehicle: simulation of human consumption of 0.5 or 5 kg of food for the GPPS and the HIPS samples and 0.5 or 3.15 kg of food for the EPS samples
- Amount of vehicle (if gavage): 10 ml
- Lot/batch no. (if required):
- Purity:
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 days
Frequency of treatment:
twice daily
Duration of test:
5 days
Doses / concentrations
Remarks:
Doses / Concentrations:
low and high, not further specified
Basis:
no data
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Statistics:
Two sided Dunnett-test (p≤0.05 and p≤0.01)

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 0.007 mg/kg bw/day
Sex:
female
Basis for effect level:
other: polystyrene dimers applied
Dose descriptor:
NOAEL
Effect level:
>= 0.015 mg/kg bw/day
Sex:
female
Basis for effect level:
other: polystyrene trimers applied

Observed effects

No unscheduled deaths occured. No abnormal clinical or necropsy findings were observed during the study. The positive control group had significantly reduced (p≤0.01) body weight gain for the entire treatment period, as compared to the untreated and vehicle control groups. None of the 23 polystyrene oligomer migrates tested at low and high doses demonstrated biologically important or statistically significant differences from the untreated or vehicle control group values for absolute or relative (to body weight) uterine weights. Based on these data, it is concluded that low and high doses of the 23 polystyrene oligomer migrates tested did not induce an estrogenic response.

Applicant's summary and conclusion