4-tert-butylbenzaldehyde

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific principles.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

Testicular toxicity screening test: The test material was administered orally to 4 groups of rats at doses from 6.5 to 50 mg/kg bw for 5 consecutive days.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylbenzaldehyde

EC Number:

213-367-9

EC Name:

4-tert-butylbenzaldehyde

Cas Number:

939-97-9

Molecular formula:

C11H14O

IUPAC Name:

4-tert-butylbenzaldehyde

Details on test material:

- Name of test material (as cited in study report): p-tert-butylbenzaldehyde
- Analytical purity: no data given

Test animals

Species:

rat

Strain:

other: SPF albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 156-220 g
- Housing: two animals per cage during dosing period, after treatment in a metabolic cage for 24 h
- Diet: not specified, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 45-65 %
- Air changes: air-conditioned room
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: rape oil

Details on exposure:

Animals were randomly allocated to test groups by means of a random table.
The test material and the respective control was administered by gavage using a metal stomach tube once daily for 5 consecutive days at a dose volume of 10 ml/kg bw.

Details on mating procedure:

only male rats were used

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5 days

Frequency of treatment:

once daily

Details on study schedule:

only male animals were used and there was no mating

Doses / concentrations

Remarks:

Doses / Concentrations:
6.5, 12.5, 25 and 50 mg/kg bw/d
Basis:
nominal conc.

No. of animals per sex per dose:

test group: 8 males
control group: 4 males

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: 1 day
After the 5th treatment, urine was collected for 24 hours.

Examinations

Parental animals: Observations and examinations:

Mortality, clinical symptoms and body weight were observed and recorded daily during the treatment period and on the 6th test day.

Oestrous cyclicity (parental animals):

not applicable

Sperm parameters (parental animals):

not assessed

Litter observations:

not applicable

Postmortem examinations (parental animals):

Gross necropsy was performed after the 6th day on all rats. Liver, kidneys and testes were weighed. Liver/kidneys were fixed in 4% formol and embedded in PARAPLAST PLUS (no furhter assessment). Testes were fixed in mixture of Bouin, embedded in PARAPLAST PLUS, sectioned at a nominal thickness of 5µm and stained with haematoxylin/eosin
The testes of all rats were microscopically examined.
The condition of the seminiferous tubules was evaluated semiquantitative by examination/grading of 100 randomly selected, cross-sectioned tubules in a respective testis section.

Postmortem examinations (offspring):

not applicable

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Mortality and general observation:
All animals survived the experimental period. 3 rats treated with 12.5 mg/kg bw/d showed slight aggressiveness on test days 3 and 4. From days 3 to 6, a slight loss of hair was seen in one animal of the 50 mg/kg bw/d group.

Body weight development:
The test material did not affect the weight development of those animals treated with 6.5 and 12.5 mg/kg bw/d. Rats treated with 25 mg/kg bw/d initially showed a slight weight loss and returned to normal at the end of the treatment. The animals of the highest dose group had a severe weight loss throughout the study.

Necropsy and organ weights:
During the dissection, a marbled liver was recorded in 2 rats treated with 50 mg/kg bw/d. In one rat treated with 25 mg/kg bw/d a small dell was seen in the right kidney.
Testes weights of rats treated with 50 mg/kg bw/d were significantly lower than these recorded for the controls.

Histology:
The changes of testes caused by the treatment were circumscribed on the seminiferous epithelium. Interstitial cells and Sertoli cells were unaffected.
The following changes were seen: disorganisation of the epithelial structure, degeneration of cells, and reduction of the spermatozoa. A testis of a control rat showed about 80 % convoluted tubules with a normal epithelium (graduation 0) and about 20 % convoluted tubules with a normal epithelium but with degenerated cells or detritus in the lumina (graduation 1). This ratio occurred in the 6.5 and 12.5 mg/kg bw/d group, too. An alteration of this ratio was seen from the 25 mg/kg bw/d group on. Moderate to severe injuries were discovered in the seminiferous epithelia of all rats treated with 50 mg/kg bw/d.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

12.5 mg/kg bw/day

Sex:

male

Basis for effect level:

other: reduced mean weight of testes; changes of the seminiferous epithelium

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Table 1: Mean body weights (g) of the rats from day 1 to day

Dose (mg/kg bw)	day 1	day 2	day 3	day 4	day 5	day 6
0	212	216	220	225	227	227
6.5	206	210	215	218	220	222
12.5	207	208	211	214	215	218
25	211	208	209	214	214	217
50	206	198	195	196	198	197

Table 2: Mean organ weights (g) of the rats

Dose (mg/kg bw/d)	testis	kidney	liver
0	2.576 ± 0.232	1.897 ± 0.113	10.69 ± 0.57
6.5	2.522 ± 0.101	1.974 ± 0.075	10.82 ± 0.49
12.5	2.570 ± 0.191	1.800 ± 0.152	10.34 ± 0.92
25	2.485 ± 0.203	1.807 ± 0.152	10.86 ± 0.76
50	2.206 ± 0.199	1.749 ± 0.076	10.11 ± 0.63

 

 

Concentration                 Grading mean %*
(mg/kg bw)           0       1       2       3
-------------------------------------------------------
control            78.1    21.9      0       0
6.5                82.5    17.5      0       0
12.5               83.0    17.0      0       0
25.0               53.6    34.6     5.7     6.1
50.0                1.5    27.6    43.8    27.1
-------------------------------------------------------
*examination/grading of 100 randomly selected, cross-sectioned tubules in a  
respective testis section.