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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: 20 week repeated dose toxicity study
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: Reliability 2 is assigned in view of its use for read across and because not all fertility parameters have been measured in the 20 week repeated dose study of alpha-Terpinyl Acetate
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Food Flavourings and Compounds of Related Structure. II. Subacute and Chronic Toxicity
Author:
Hagan et al.
Year:
1967
Bibliographic source:
Hagan E.C., Hansen W.H., Fitzhugh O.G., Jenner P.M., Jones W.I., Taylor J.M., Long E.L., Nelson A.A., and Brouwer J.B. (1967) Food Flavourings and Compounds of Related Structure. II. Subacute and Chronic Toxicity. Food Cosm Toxicology, 5, 141-157.  

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD TG 408
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Osborne-Mendel

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
See repeated dose section
Details on mating procedure:
There is information on male and female gonads.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
20 weeks
Frequency of treatment:
daily
Details on study schedule:
See repeated dose section.
No. of animals per sex per dose:
See repeated dose section
Details on study design:
See repeated dose section.

Examinations

Parental animals: Observations and examinations:
See repeated dose section.
Oestrous cyclicity (parental animals):
No
Sperm parameters (parental animals):
No
Litter observations:
No
Postmortem examinations (offspring):
No
Statistics:
No
Reproductive indices:
No
Offspring viability indices:
No

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not examined
Description (incidence and severity):
Only when macroscopic effects were seen.
Other effects:
effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 314 mg/kg bw/day (actual dose received)
Based on:
other: The result is converted from alpha-Terpinyl Acetate into alpha-Terpineol using their molecular weights.
Sex:
male/female
Basis for effect level:
other: The animals were dosed via the diet with alpha-Terpinyl Acetate: 1000, 2500 and 10000 ppm, resulting in 400 mg/kg bw

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEL for fertility from this test is >= 400 mg/kg bw for alpha-Terpinyl Acetate, resulting in 314 mg/kg bw for alpha-Terpineol when using a correction for molecular weight (154/196)
Executive summary:

In repeated dose dietary study of 20 weeks, similar to OECD TG 408, with alpha-Terpinyl Acetate no effect on male and female gonads were seen at the highest dose of 400 mg/kg bw, resulting in a NOAEL of >= 400 mg/kg bw, resulting in a NOAEL for alpha-Terpineol of >=314 mg/kg bw when using a correction for molecular weight (154/196).