Reaction mass of (R*,R*)-7-methoxy-3,7-dimethyl-2-octanol and (R*,S*)-7-methoxy-3,7-dimethyl-2-octanol

Endpoint summary

Description of key information

The oral LD₅₀ of the test substance is >2000 mg/kg bw in rats.

The dermal LD₅₀ of the test substance is > 2000 mg/kg bw in rats

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 May - 01 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 423 without any deviation

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

dated 17 December, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

23 October 2015

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 200-212 g
- Fasting period before study: Food was removed on Day 1 and then redistributed 4 hours after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Foodstuff (A04, SAFE), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25°C
- Humidity: 30-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.22 mL/kg bw

DOSAGE PREPARATION: In the first and the second step of the study, the test item was administered by gavage under a volume of 2.22 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.899 g/mL at 20°C supplied by the sponsor) using a suitable graduated syringe fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

other: historical control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 30 minutes, 1 hour, 3 hours, 4 hours, and then once daily for 14 days. Animals were weighed on Day D0 (just before administering the test item) and then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 and macroscopic observations were noted.

Statistics:

No data

Preliminary study:

Not applicable

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: A decrease or an absence in spontaneous activity (6/6), muscle tones (5/6), righting reflex (6/6), Preyer's reflex (5/6), associated with piloerection (2/6), an increase of salivation (6/6), partial or total ptosis (6/6), an hypothermia (2/6), tremors (2/

Gross pathology:

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

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance is >2000 mg/kg bw in rats. Therefore it is not classified according to Regulation (EC) No 1272/2008. No signal word or hazard statement is required.

Executive summary:

In an acute oral toxicity study performed according to Guideline OECD 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was given by oral gavage to a group of 6 female Sprague Dawley rats. Animals were then observed for mortality, body weight changes and clinical signs of toxicity for 14 days.

No mortality occurred during the study. A decrease or an absence in spontaneous activity (6/6), muscle tones (5/6), righting reflex (6/6), Preyer's reflex (5/6), associated with piloerection (2/6), an increase of salivation (6/6), partial or total ptosis (6/6), an hypothermia (2/6), tremors (2/6), and myosis (4/6) were noted during the first hours of the test. The animals recovered a normal activity at 24-hour post dose. The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Therefore, the oral LD50 of the test substance is >2000 mg/kg bw in rats and it is not classified according to Regulation (EC) No 1272/2008. No signal word or hazard statement is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study conducted according to OECD TG 423

Acute toxicity: via inhalation 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:

17-31 May 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 402 without any deviation

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

dated 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

dated 30 May 2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

23 October 2015

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS, France
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 7 or 8 weeks
- Weight at study initiation: 239-256 g (males); 197-212 g (females)
- Housing: On Day 1 of the study, animals were housed by group of five in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. During the treatment, the animals were kept in individual cages.
- Diet (e.g. ad libitum): Foodstuff (SAFE - A04), ad libitum
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25°C
- Humidity: 30-70%
- Air changes: At least 10/hour
- Photoperiod: 12 hours dark / 12 hours light

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of the trunk (50 mm X 50 mm)
- % coverage: At least 10% of the body surface area
- Type of wrap if used: Animals from treated groups received the topical application of the test material under non occlusive 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
- Time after start of exposure: 24 hours
- Washing (if done): After removal of the gauze dressings, the treated area was rinsed with distilled water and liquid paraffin.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.22 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: historical control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded at 1 hour, 3 hours, 5 hours, and then once daily for 14 days. Animals were weighed on Day D0 (just before administering the test item) and then on Day 2, Day 7, and Day 14.
- Necropsy of survivors performed: Yes; animals were euthanized with sodium pentobarbital on Day 14 and macroscopic observations were noted.

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: erythema was noted in all animals at 24-hour post-dose and was totally reversible on Day 4.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs related to the administration of the test substance were observed.

Gross pathology:

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

Other findings:

Erythema was noted in all animals at 24-hour post-dose and was totally reversible on Day 4.

None

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of the test substance is > 2000 mg/kg bw in rats therefore it is not classified according to the Regulation (EC) N° 1272/2008. No signal word or hazard statement is required.

Executive summary:

In an acute dermal toxicity study performed according to Guideline OECD 402 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was applied onto the intact skin of 5 male and 5 female Sprague Dawley rats under occlusive conditions for 24 hours. Animals were then observed for mortality, dermal reactions, body weight changes and clinical signs of toxicity for 14 days.

No mortality occurred during the study. No systemic clinical signs related to the administration of the test substance were observed. Erythema was noted in all animals at 24-hour post-dose and was totally reversible on Day 4. Body weight gain of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment-related changes.

Therefore, the dermal LD50 of the test substance is > 2000 mg/kg bw in rats and it is not classified according to Regulation (EC) N° 1272/2008. No signal word or hazard statement is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study conducted according to OECD TG 402

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the OECD Guideline 423 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was given by oral gavage to a group of 6 female Sprague Dawley rats. Animals were then observed for mortality, body weight changes and clinical signs of toxicity for 14 days. No mortality occurred during the study. A decrease or an absence in spontaneous activity (6/6), muscle tones (5/6), righting reflex (6/6), Preyer's reflex (5/6), associated with piloerection (2/6), an increase of salivation (6/6), partial or total ptosis (6/6), an hypothermia (2/6), tremors (2/6), and myosis (4/6) were noted during the first hours of the test. The animals recovered a normal activity at 24-hour post dose. The body weight evolution of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. Rat Oral LD50 >2000 mg/kg bw.

Acute dermal toxicity:

In an acute dermal toxicity study performed according to the OECD Guideline 402 and in compliance with GLP, a single dose of 2000 mg/kg bw of the test substance was applied onto the intact skin of 5 male and 5 female Sprague Dawley rats under occlusive conditions for 24 hours. Animals were then observed for mortality, dermal reactions, body weight changes and clinical signs of toxicity for 14 days. No mortality occurred during the study. No systemic clinical signs related to the administration of the test substance were observed. Erythema was noted in all animals at 24-hour post-dose and was totally reversible on Day 4. Body weight gain of the animals remained normal throughout the study. The macroscopic examination of the animals at the end of the study did not reveal any treatment-related changes. Rat Dermal LD50 >2000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity:

The oral LD50 of the registered substance is >2000 mg/kg bw in rats. Therefore it is not classified according to the Regulation (EC) No 1272/2008. No signal word or hazard statement is required.

Acute dermal toxicity:

The acute dermal LD50 of the registered substance is higher than 2000 mg/kg bw in rats and porbably higher than 5000 mg/kg bw therefore it is not classified according to the CLP regulation EC No 1272/2008.