Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: similar to guideline study (range-finding study for a prenatale development toxicity study OECD 414)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
range-finding study
Principles of method if other than guideline:
5 animals/dose
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-methyl-l-butanol
- Test substance No. 88/56 [H 21670]
- Physical state: liquid/colourless
- Analytical purity: 98.6% (acc. toreport Feb 2, 1988)
- Stability under test conditions: The stability was ensured for the study period under the specified storage conditions by reanalysis ( see report of Nov 25, 1988)
- Storage condition of test material: at roomtemperature

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: female Wistar rats (strain: SPF-Wistar/Chbb:THOM; breeding facilities: Dr. K. Thomae GmbH, D-7950 Biberach/Riss, FRG). The animals were free from any clinically evident signs prior to the beginning of the study.
- Age at study initiation: ca 11 weeks
- Weight at study initiation: ca 216 g
- Housing: singly in wire cages (type D III of Becker & Co, Castrop-Rauxel, FRG)
- Diet (e.g. ad libitum): KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, CH-4303 Kaiseraugst, Switzerland; during the exposure-free observation period
- Water (e.g. ad libitum): tap water; during the exposure-free observation period
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the animals were exposed singly in wire cages (D III) in glass-steel inhalation chambers (manufacturer: BASF Aktiengesellschaft), Volume Vz 1,100 1 (test group 1, 2 and 3), Volume V 2 1,600 1 (test group 0 and parts of the test groups during the preflow period).
- Method of holding animals in test chamber: whole-body exposure system (glass-steel inhalation chamber) with a volume of about 1.1 m3 (test groups 1 - 3); volume of the inhalation chamber of the control group: 1.6 m3
- Source and rate of air: the test substance was supplied by means of two continuously driven piston pumps (Unita, Braun) in test
group 1, a continuously metering pump (Optimat MP) in test group 2, and another continuously metering pump (Desaga) in test gorup 3 to a vaporizer heated with a circulating thermostat and evaporated. The evaporation temperatures are shown in the following table.

_______________________________________________________________________________
Test group /ml/hour /Evaporation temperature (°C) /Supply air (l/hour) /Exhaust air (l/hour)
-----------------------------------------------------------------------------------------------------------------------
0 /Fresh air /- /30000 /29500
1 /13.7 - 14.3 /50 /21500 /22000
2 /75.6 - 82.8 /60 /21500 /22000
3 /295 - 305 /70 /21500 /22000
_______________________________________________________________________________

A stream of fresh air measured with a rotameter took up the vapors. A further stream of fresh air was passed in downstream of the vaporizer. After passing through a mixing device, this mixture of vapors and air was supplied to exposure system

- Temperature, humidity, pressure in air chamber: the pressure in the inhalation chambers was measured continuously (inclined manometer) and recorded, as a rule, 3 times/exposure. Conditioned supply air ( about 50% humidity, 22 °C) was used for the exposure in all test groups. The temperature in the exposure systems was measured continuously (digital thermometer, Diehl) and recorded, as a rule, 3 times/exposure. The relative humidity in the chambers was checked with a humidity measuring probe (Vaisala) at least once a day and also recorded.
- Air flow rate: all air flows, supply air and exhaust air were adjusted by means of flowmeters (rotameter) for all test groups and recorded, as a rule, 6 times/exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: the concentration in the inhalation chambers was monitored by means of a GC-method. The concentrations of the test groups were analyzed by gas chromatography after absorption of MEB samples in 2-propanol.
The gas chromatographs were calibrated with weighed amounts of the test substance.
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
gas chromatograph monitoring
Duration of treatment / exposure:
gestational days 6 - 15
Frequency of treatment:
6 hours/day
Duration of test:
20 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.5, 2.5, 5.0 mg/l
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.53 ± 0.007, 2.50 ± 0.11 and 5.1 ± 0.16 mg/l
Basis:
analytical conc.
gas chromatograph monitoring
No. of animals per sex per dose:
10 (5 in the main groups, 5 in the satellite groups)
Control animals:
yes, concurrent no treatment
Details on study design:
- Other: cesarean of dams at days 20 p.c.

Examinations

Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: the behavior and state of health of the test animals were checked on workdays at least 3 times on exposure days and, as a rule, once during the post-exposure observation period.

POST-MORTEM EXAMINATIONS: Yes
- Organs examined: gross patology including placenta weights

OTHER: a check for dead animals was made daily. hematologically examination in the satellite groups
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes:

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEC
Effect level:
5 mg/L air (nominal)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

Dose descriptor:
NOAEC
Effect level:
5 mg/L air (nominal)
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Dams: no clinical symptoms seen. At 5.1 mg/l it was unclear if a slight retardation of body weight increase occurred. Haematology and clinical-chemical examinations did not show any substance-related effects. Reproductive parameters, fetal and placental weights were unchanged. Fetuses did not show any macroscopic changes.

Applicant's summary and conclusion