p-menth-1-en-8-ol

Endpoint summary

Description of key information

Acute oral toxicity: Weight of evidence. Read across approach: Based on the read-across approach from the analogue alpha terpineol, the acute oral LD50 value of laevo alpha terpineol in mice is determined to be 2830 mg/kg bw.

Acute oral toxicity: Weight of evidence. Read across approach: Based on the read-across approach from the analogue alpha terpinyl acetate, the LD50 of laevo alpha terpineol is calculated to be 3988 mg/kg body weight by oral route in the rat.

Acute inhalation toxicity: Data waiving (study scientifically not necessary): According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information is provided for dermal route.

Acute dermal toxicity: Key study: The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Method similar to OECD guideline 423, but no information on doses were reported

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No information on tested doses

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: young adults rats
- Fasting period before study: 18 h
- Housing: cages
- Diet (e.g. ad libitum): Food was replaced in cages as soon as animals received their doses.
- Water (e.g. ad libitum): Ad libitum.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Not reported

No. of animals per sex per dose:

5 females and 5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 2 weeks
- Necropsy of survivors performed: no specified
- Other examinations performed: clinical signs, body weight and time of death

Statistics:

LD50 were computed by the method of Litchfield & Wilcoxon (1949).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 075 mg/kg bw

Based on:

test mat.

95% CL:

>= 4 160 - <= 6 190

Mortality:

Death time: 4 hr-5 days

Clinical signs:

other: Depression, scrawny appearance, porphyrin-like deposits around eyes and nose.

Gross pathology:

no data

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

The LD50 of the test item is 5075 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test compound was tested following a method similar to OECD Test Guideline 401. Ten young adult Osborne-Mendel rats evenly divided by sex were administered by oral gavage.

Animals were observed for 2 weeks during which time the development of toxic signs was followed and time of death recorded. Animals exposed to terpinyl acetate alpha showed depression, scrawny appearance, and porphyrin-like deposits around eyes and nose. The acute oral LD50 of the test item was determined to be 5075 mg/kg bw (95% confidence limits: 4160 -6190 mg/kg bw).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

(It is published in a peer reviewed journal but with limitations in design and/or reporting, e.g., it was conducted in mice instead of rats or the lack of data on number of animals used or doses administered)

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The test substance was administered by gavage to groups of 10 male dd-K mice. From the number of deaths during a 7 day observation period after the administration of the drug, the LD50 value was calculated by the Litchfield-Wilcoxon method.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: dd-k

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 25 g
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

no data

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days

Statistics:

Litchfiel-Wilcoxon method

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 830 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 290 - <= 3 497

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

The acute oral LD50 value in mice was reported to be 2830 mg/kg bw (95% CI = 2290-3497).

Executive summary:

Alpha-Terpineol was administered by gavage to groups of 10 male dd-K mice. From the number of deaths during a 7 day observation period after the administration of the test substance, the LD50 value was calculated by the Litchfield-Wilcoxon method. The oral acute toxicity of the test substance was 2830 mg/kg bw (95% CI = 2290 -3497).

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance alpha terpinyl acetate undergoes rapid hydrolysis to acetic acid and alpha terpineol which shares the same functional groups with the substance L-alpha terpineol and also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 988 mg/kg bw

Based on:

other: Read-across from an analogue

95% CL:

>= 3 269 - <= 4 864

Remarks on result:

other: read-across from an analogue for which LD50 = 5075 mg/kg bw

Mortality:

Death time: 4 hr-5 days

Clinical signs:

other: Depression, scrawny appearance, porphyrin-like deposits around eyes and nose.

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

Based on the read-across approach from the analogue alpha terpinyl acetate, the LD50 of laevo alpha terpineol is calculated to be 3988 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the alpha terpinyl acetate was tested following a method similar to OECD Test Guideline 401. Ten young adult Osborne-Mendel rats evenly divided by sex were administered by oral gavage. Animals were observed for 2 weeks during which time the development of toxic signs was followed and time of death recorded. Animals exposed to terpinyl acetate alpha showed depression, scrawny appearance, and porphyrin-like deposits around eyes and nose. The acute oral LD50 of the test item was determined to be 5075 mg/kg bw (95% confidence limits: 4160 -6190 mg/kg bw). Based on these results, the read-across approach was applied and the acute oral LD50 of laevo alpha terpineol is determined to be 3988 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue substance alpha terpineol which shares the same functional groups with the substance L-alpha terpineol also has comparable values for the relevant molecular properties.
See attached the reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 830 mg/kg bw

Based on:

other: Read-across from an analogue

95% CL:

>= 2 290 - <= 3 497

Remarks on result:

other: read-across from an analogue for which LD50 = 2830 mg/kg bw

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

Based on the read-across approach from the analogue alpha terpineol, the acute oral LD50 value of laevo alpha terpineol in mice is determined to be 2830 mg/kg bw.

Executive summary:

Alpha-Terpineol was administered by gavage to groups of 10 male dd-K mice. From the number of deaths during a 7 day observation period after the administration of the test substance, the LD50 value was calculated by the Litchfield-Wilcoxon method. The oral acute toxicity of the test substance was 2830 mg/kg bw (95% CI = 2290 -3497). Based on these results, the read-across approach was applied and the acute oral LD50 of laevo alpha terpineol is determined to be 2830 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 830 mg/kg bw

Quality of whole database:

Weight of evicence from two studies with Klimisch score = 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII, column 2: In addition to the oral route (Annex VII, 8.5.1.), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information is provided for dermal route.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 May 2018 - 29 May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(SPF Caw)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 218.3 g (SD = 24.7 g)
- Fasting period before study: not specified.
- Housing: During the treatment, the animals were kept in individual cages. On D1, the animals were put together into their cage. The rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains dust free wood shavings which were changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet (e.g. ad libitum): Ad libitum. Teklad Global 16% Protein Rodent Diet (ENVIGO 2016).
- Water (e.g. ad libitum): Ad libitum. Drinking water (tap-water from public distribution system). Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE).
- Acclimation period: the animals were acclimatized for at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19ºC to 25ºC
- Humidity (%): 30 to 70%
- Air changes (per hr): >10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light (07.00 to 19.00) and 12 hours dark cycle.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: at least 10% of the body surface area.
- Type of wrap if used: porous gauze dressing (50 mm x 50 mm non-woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic microporeTM adhesive tape from 3M).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.18 mL/kg body weight
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A

Duration of exposure:

24 h

Doses:

Range finding study: 2000 mg/kg body weight
Main study: 2000 mg/kg body weight

No. of animals per sex per dose:

Range finding study: 1 female per dose
Main study: 2 females per dose

Control animals:

yes

Remarks:

(study performed on three females receiving distilled water by topical application under requirements of OECD Guideline 402)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At each step, the animals were observed three times on test day 0 (day of administration), i.e. at T0+30 min, T0+3h and T0+5h, and once daily during days 1 to 14 post administration. The body weights were recorded on test day 0 (just before administration) then on D2, D7, and D14.
- Necropsy of survivors performed: yes. At termination, gross pathological findings were recorded and reported.
- Other examinations performed:
Clinical observations: spontaneous activity, Preyer’s reflex (noise), respiratory rate, convulsions, tremors, body temperature, muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex and treatment site (erythema, dryness of the skin, scab, etc.)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: Erythema was noted in treated animals (2/3) at 48 hours post dose and was totally reversible on day 6. Dryness of the skin was noted in treated animals (2/3) on day 5 and on day 8. Scab was noted in treated animals (2/3) between days 6 and 7.

Gross pathology:

The macroscopic examination of the animal at the end of the study did not reveal treatment-related changes.

Table 1: Body weight and weight gain in grams

FEMALES	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf2515	190	225	35	243	53	277	87
Rf2568	235	239	4	251	16	271	36
Rf2569	230	241	11	268	38	290	60
MEAN	218.3	235.0	16.7	254.0	35.7	279.3	61.0
Standard deviation	24.7	8.7	16.3	12.8	18.6	9.7	25.5

Interpretation of results:

other: No category (CLP Regulation EC no. 1272/2008)

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.

Executive summary:

The acute dermal toxicity of the test item was studied according to OECD Guideline 402 (GLP study). 3 female Sprague-Dawley rats were tested for a exposure period of 24 h. Initially, a range finding study was conducted at a single dose of 2000 mg/kg bw in one animal. Based on the results of range finding two additional rats were tested at a dose of 2000 mg/kg bw. No mortality was observed. The body weight evolution of the animals remained normal during the study. Erythema was noted in treated animals (2/3) at 48 hours post dose and was totally reversible on day 6. Dryness of the skin was noted in treated animals (2/3) on day 5 and on day 8. Scab was noted in treated animals (2/3) between days 6 and 7. No other clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal any treatment related effects. Based on these results, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Key study with Klimisch score = 1

Additional information

Acute oral toxicity: Weight of evidence. Read across approach: Alpha-Terpineol was administered by gavage to groups of 10 male dd-K mice. From the number of deaths during a 7 day observation period after the administration of the test substance, the LD50 value was calculated by the Litchfield-Wilcoxon method. The oral acute toxicity of the test substance was 2830 mg/kg bw (95% CI = 2290 -3497). Based on these results, the read-across approach was applied and the acute oral LD50 of laevo alpha terpineol is determined to be 2830 mg/kg bw.

Acute oral toxicity: Weight of evidence. Read across approach: The acute oral toxicity of the alpha terpinyl acetate was tested following a method similar to OECD Test Guideline 401. Tenyoung adult Osborne-Mendel rats evenly divided by sexwere administered by oral gavage.Animals were observed for 2 weeks during which time the development of toxic signs was followed and time of death recorded. Animals exposed to terpinyl acetate alpha showed depression, scrawny appearance, and porphyrin-like deposits around eyes and nose. The acute oral LD50 of the test item was determined to be 5075 mg/kg bw (95% confidence limits: 4160 -6190 mg/kg bw). Based on these results, the read-across approach was applied and the acute oral LD50 of laevo alpha terpineol is determined to be 3988 mg/kg bw.

Acute inhalation toxicity: Data waiving (study scientifically not necessary):According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The information is provided for dermal route.

Acute dermal toxicity: Key study: The acute dermal toxicity of the test item was studied according to OECD Guideline 402 (GLP study). 3 female Sprague-Dawley rats were tested for a exposure period of 24 h. Initially, a range finding study was conducted at a single dose of 2000 mg/kg bw in one animal. Based on the results of range finding two additional rats were tested at a dose of 2000 mg/kg bw. No mortality was observed. The body weight evolution of the animals remained normal during the study.Erythema was noted in treated animals (2/3) at 48 hours post dose and was totally reversible on day 6. Dryness of the skin was noted in treated animals (2/3) on day 5 and on day 8. Scab was noted in treated animals (2/3) between days 6 and 7. No other clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal any treatment related effects. Based on these results, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.