6-tert-butyl-m-cresol

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted study, carried out by Hatano Research Institute, Food and Drug Safety Center (JAPAN)

Data source

Reference

Reference Type:

publication

Title:

Toxicity Testing Report of Environmental Chemicals 7, 179-181

Author:

MHW (Ministry of Health and Welfare), Japan .

Year:

1999

Bibliographic source:

cited: OECD SIDS Initial Assessment Report, Boston 20-25th Oct. 2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD TG 422

Principles of method if other than guideline:

Type: Toxicity to Reproduction
Method : OECD Preliminary Reproduction Toxicity Screening Test (TG 422)

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

6-tert-butyl-m-cresol

EC Number:

201-842-3

EC Name:

6-tert-butyl-m-cresol

Cas Number:

88-60-8

Molecular formula:

C11H16O

IUPAC Name:

2-tert-butyl-5-methylphenol

Details on test material:

Produced by Sumitomo Chemical, Lot No.1271012. Purity 99.23%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Male: for 42 days;
Female: for 40-48 days from 14 days prior to mating to the 3 day of lactation

Frequency of treatment:

Daily

Duration of test:

Terminal killing: Male; day 43 Female; day 4 of lactation

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 2.5, 12.5, 60 mg/kg/day (in corn oil)
Basis:
nominal conc.

No. of animals per sex per dose:

No. of animals per sex per dose: 13 per sex per dose group

Control animals:

yes, concurrent vehicle

Details on study design:

[Study Design]
The animals were sacrificed on the day 4 of lactation for females. Females with no delivery were killed on the day 25 of pregnancy. *Satellite groups and reason they were added: none *Mating procedure: Male / female per cage; 1/1, length of cohabitation; at most 14 days, until proof of copulation (formation of vaginal plug or sperm detection in vagina)

Statistics:

Statistical methods: Dunnett's or Scheffe's test for continuous data and Chisquare test for quantal data

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

12.5 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: for maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

12.5 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: for pups toxicity

Observed effects

*Mortality and day of death: the death was not observed in any group
*Body weight: suppression of body weight gain was observed on the day14 of pregnancy and the day 4 of lactation in the 60 mg/kg group.
*Food consumption: Decrease in food consumption was observed during lactation period in 60 mg/kg group.
*Pups data: Grossly visible abnormalities : no significant effect was observed.

Any other information on results incl. tables

NOAEL;
12.5 mg/kg/day for maternal toxicity
12.5 mg/kg/day for pups toxicity.
*Maternal data with dose level (with NOAEL value):
Decrease tendencies, not significant, in number of corpora lutea and  number of implantation sites were observed in the 60 mg/kg group.
*Pups data with dose level (with NOAEL value): Decrease in number of live  pups at the day 0 and 4 of lactation were observed at 60 mg/kg group.  Decrease in body weights of both sexes on the day 0 and 4 of lactation  were noted in the 60 mg/kg group.

Dose level (mg/kg/day)  0        2.5     12.5     60
No. of pairs mated     13       13       13       13
No. of pregnant females12       13       13       12
Corpora lutea          16.4±1.8 17.0±0.7 16.5±4.6 14.0±2.4
Implantation scars     14.8±3.2 16.2±1.5 15.0±4.6 12.8±3.2
Pups born              13.8±3.0 15.5±1.6 13.8±4.3 10.5±3.1
Delivery index(% )     93.5±6.2 95.2±4.2 92.4±7.4 83.3±17.9
Live pups born         13.8±3.0 15.3±1.6 13.5±4.4 10.3±2.9*
Live birth index (% ) 100±0.0   99.0±3.5 91.0±27.898.1±3.5
Live pups on day 4 of lactation
                       13.5±2.8 14.1±4.5 14.4±1.7 8.8±3.7*

Body weight of live pups (g)
on day 0
Males                   7.0±0.7 6.6±0.4 6.8±0.8 5.8±1.2**
Females                 6.7±0.6 6.8±1.4 6.3±0.7 5.6±1.3**
on day 4
Males                  11.3±1.5 10.9±1.0 10.2±1.5 9.6±2.5*
Females                11.0±1.6 10.4±1.0 9.5±1.2 8.8±2.9**
(*P<0.05, **P<0.01)

Applicant's summary and conclusion

Executive summary:

method: 2 -tert-buty-5 -methylphenol was administered to SD(Crj:CD) rats by gavage at doses of 0 (vehicle ; corn oil) 2.5, 12.5 and 60 mg/kg from 14 days before mating to 14 days after mating in males and from 14 days before mating to day 3 of lactation in females. result: Maternal body weight gain and food consumption were suppressed in the 60 mg/kg group. No adverse effects were observed on copulation, fertility, delivery and lactation in any group. Slight effects to the maternal reproductive index, such as a slight decrease in the number of corpora lutea, implants, number of live neonates at birth and a slight low value of delivery index were observed at 60 mg/kg. In this dose group, the body weight gain of pups was suppressed. Evidence of malformations was not observed grossly at any dose group. based on the above results, the NOAEL for reproductive toxicity is considered to be 12.5 mg/kg for both female parents and pups reference: MHW, Japan (1999)