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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. QA statement)
Justification for study design:
The study was designed to evaluate the potential toxic effect of the test item Gamma Terpinene when administered to rats for a minimum of 28 days and to evaluate the potential of the test item to affect male and female reproductive performance such as gonadal function, mating behaviour, conception, parturition, and early postnatal development. The study was performed in compliance with the OECD Test Guideline No.422, Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test, Adopted: 29 July, 2016.

Test material

Constituent 1
Chemical structure
Reference substance name:
p-mentha-1,4-diene
EC Number:
202-794-6
EC Name:
p-mentha-1,4-diene
Cas Number:
99-85-4
Molecular formula:
C10H16
IUPAC Name:
p-mentha-1,4-diene
Specific details on test material used for the study:
Clear, liquid.
Storage: Room temperature (20 ± 5°C); keep away of light

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Duration of treatment / exposure:
28d
Frequency of treatment:
Females were treated during:
 14-day pre-mating,
 14-day mating (maximum)
 22-day gestation (approximately)
 13-day lactation
Males were treated during:
 14-day pre-mating,
 14-day mating (maximum)
The animals designated for post-treatment observation (5 animals per sex in control and high groups, respectively) remained untreated for subsequent 14 days.
Doses / concentrationsopen allclose all
Dose / conc.:
25 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Description (incidence and severity):
There were no test item-related deaths of animals during the study. Animals lived through the observation period without significant visible clinical signs.
Lethargy in 2 males (ID 4-Control and 33-Mid) was observed on Day 7 of treatment. Lethargy, spasm and tremor was observed in females: ID 102, 103, 108 (High) and ID 84, 89, 63 (Mid) between Day 4 and Day 7 of treatment. No other signs were observed.
Mortality:
no mortality observed
Description (incidence):
There were no test item-related deaths of animals during the study. Animals lived through the observation period without significant visible clinical signs.
Body weight and weight changes:
not specified
Description (incidence and severity):
The body weight of males of all dose groups was mildly increasing during the study. No significant differences between control and dose groups were observed. The body weight of High dose satellite males was similar in comparison with recovery control males during the whole study.
The body weight of females of all dose groups was mildly increasing during the study. Only significant difference between Control group and Low group on Day1 of the treatment in females was noticed. The body weight of recovery High dose females was similar in comparison with recovery control females during the whole study.
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
Food consumption of males of all dose groups was similar to the control males during the whole study. Food consumption of recovery treated males was similar in comparison with control group during the whole application and recovery period.
Food consumption of treated females was similar or slightly lower in comparison with control group during the whole application period. Food consumption of recovery treated females was similar in comparison with recovery control females for the whole study.
Haematological findings:
not specified
Description (incidence and severity):
Only statistically significant decrease of haemoglobin in males of High group and females of Mid group against Control group were registered. These sporadic changes had no dose relationship; they were considered to be a result of intra-individual and inter-individual variability for this species or they have only statistical character.
No test item related effect on the haematology parameters were observed in this study. During the study, haematology parameters in both sexes were within or close to the historical control data for this species.
Clinical biochemistry findings:
not specified
Description (incidence and severity):
There were no findings in clinical chemistry parameters which could be definitively attributed to the treatment.
Statistical evaluation of clinical chemistry results showed no differences between control and dose groups. The average values of clinical chemistry parameters in all animals were within or slightly outside the serum historical control data.
Urinalysis findings:
not specified
Description (incidence and severity):
No significant changes against normal physiological conditions were detected. In the urine of some animals, small amounts of protein, ketones and presence of blood (erythrocytes) were observed. There are no differences between control and the dose groups. These findings considered to be normal (9). No test item related effect was observed.
Behaviour (functional findings):
not specified
Description (incidence and severity):
Open field test
The locomotor activity was not influenced by the administration of tested compounds in neither experimental group compared to Control.
Tail flick Test
In comparison with Control group, the reaction time was not significantly influenced by the administration of test item.
Grip Strength Test
Statistically significant difference between the Control and the Low group was observed. This significance has probably statistical character. Other differences observed within the males group were not statistically significant.
As to the group of females, male satellites and female satellites, there is not a statistically significant difference between the means of component groups.
Organ weight findings including organ / body weight ratios:
not specified

Effect levels (P0)

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
reproductive performance
Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Key result
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on the systemic toxicity

Target system / organ toxicity (P0)

open allclose all
Key result
Critical effects observed:
no
System:
urinary
Key result
Critical effects observed:
no
System:
haematopoietic

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Description (incidence and severity):
There were no test item-related deaths of animals during the study. Animals lived through the observation period without significant visible clinical signs.
Lethargy in 2 males (ID 4-Control and 33-Mid) was observed on Day 7 of treatment. Lethargy, spasm and tremor was observed in females: ID 102, 103, 108 (High) and ID 84, 89, 63 (Mid) between Day 4 and Day 7 of treatment. No other signs were observed.
Mortality / viability:
no mortality observed
Description (incidence and severity):
There were no test item-related deaths of animals during the study.
Body weight and weight changes:
not specified
Description (incidence and severity):
The body weight of males of all dose groups was mildly increasing during the study. No significant differences between control and dose groups were observed. The body weight of High dose satellite males was similar in comparison with recovery control males during the whole study.
The body weight of females of all dose groups was mildly increasing during the study. Only significant difference between Control group and Low group on Day1 of the treatment in females was noticed. The body weight of recovery High dose females was similar in comparison with recovery control females during the whole study.
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
Food consumption of males of all dose groups was similar to the control males during the whole study. Food consumption of recovery treated males was similar in comparison with control group during the whole application and recovery period.
Food consumption of treated females was similar or slightly lower in comparison with control group during the whole application period. Food consumption of recovery treated females was similar in comparison with recovery control females for the whole study.
Haematological findings:
not specified
Description (incidence and severity):
Only statistically significant decrease of haemoglobin in males of High group and females of Mid group against Control group were registered. These sporadic changes had no dose relationship; they were considered to be a result of intra-individual and inter-individual variability for this species or they have only statistical character.
No test item related effect on the haematology parameters were observed in this study. During the study, haematology parameters in both sexes were within or close to the historical control data for this species.
Clinical biochemistry findings:
not specified
Description (incidence and severity):
There were no findings in clinical chemistry parameters which could be definitively attributed to the treatment.
Statistical evaluation of clinical chemistry results showed no differences between control and dose groups. The average values of clinical chemistry parameters in all animals were within or slightly outside the serum historical control data.
Urinalysis findings:
not specified
Description (incidence and severity):
No significant changes against normal physiological conditions were detected. In the urine of some animals, small amounts of protein, ketones and presence of blood (erythrocytes) were observed. There are no differences between control and the dose groups. These findings considered to be normal (9).
Organ weight findings including organ / body weight ratios:
not specified
Description (incidence and severity):
Relative weights of the liver in the Low, Mid and High dose males were significantly increased compared to Control group. Significant increase of kidney and spleen relative weight and decrease of relative weight of thymus in High dose against Control were observed. In satellite males no differences between Control and High dose were observed. No findings were seen in females.
Gross pathological findings:
not specified
Description (incidence and severity):
All animals were necropsied. During necropsy, hydrometra and uterus filled with blood were observed in two females. No other macroscopically changes were noticed.
Histopathological findings:
not specified

Effect levels (F1)

open allclose all
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: reproduction
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Based on the reproduction toxicity
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on the systemic toxicity

Target system / organ toxicity (F1)

open allclose all
Key result
Critical effects observed:
no
System:
urinary
Key result
Critical effects observed:
no
System:
haematopoietic

Overall reproductive toxicity

Key result
Reproductive effects observed:
yes
Lowest effective dose / conc.:
250 mg/kg bw/day
Treatment related:
yes
Relation to other toxic effects:
not specified

Applicant's summary and conclusion