Reaction Mass of 1,4-dimethyl-7-(prop-1-en-2-yl)-1,2,3,4,5,6,7,8-octahydroazulene and 3,8-dimethyl-5-(prop-1-en-2-yl)-1,2,3,3a,4,5,6,7-octahydroazulene and 4,8a,9,9-tetramethyldecahydro-1,6-methanonaphthalen-1-ol

Endpoint summary

Description of key information

Acute oral toxicity
The acute median lethal oral dose (LD50) to rats of the test material was found to be > 5.0 g/kg bodyweight.
Acute inhalation
Testing by the inhalation route in accordance with column 2 of Annex VIII of 1907/2006/EC, is considered to be inappropriate as exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance (0.94 Pa at 20°C) and/or the possibility of exposure to aerosols or droplets of an inhalable size.
Acute dermal toxicity
One acute dermal study with limited detail is available that suggests LD50(dermal)>5000mg/kg bw). This is supported by an  acute oral toxicity study that suggests the substance is not acutely harmful (LD50>5000mg/kg). Potential for systemic exposure via ingestion is considered to be higher than exposure following contact with skin, therefore the existing data from exposure via contact with skin is considerd to be reliable and represents the worse case.

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:

1988-06-09 and 1988-06-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

A group of six rats (3 males and 3 females) was treated at 2.0 g/kg bodyweight and, based on the result of that dosing, a further group of six rats was dosed at 5.0 g/kg.

GLP compliance:

yes

Test type:

other: single dose

Species:

rat

Strain:

other: CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 108-142 g
- Fasting: overnight prior to dosing and for approximately 4 hours after dosing.
- Housing: grouped by sex in metal cages with wire mesh floors.
- Diet: Standard laboratory rodent diet (Labsure LAD-1) ad libitum (see Appendix 1, attached)
- Water: ad libitum (see Appendix 2, attached, for results of routine chemical examination of water at source (Grafham Final Water) as conducted by Anglian Water Authority)
- Acclimation period: 8 days prior to start of study

ENVIRONMENTAL CONDITIONS
- Temperature: 21-24 ºC
- Humidity: mean value 67 %
- Air changes: approximately 15 per hour
- Photoperiod: controlled by a time switch to provide 12 hours artificial light in each 24 hour period.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter (8 choke)

Doses:

Single dose

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Each animal was identified by cage number and ear punching.
- Each cage was identified by a coloured label displaying the dose level, study schedule number and the initials of the study director.
- Animals were observed soon after dosing and at frequent intervals for the remainder of day one (a minimum period of five hours).
- On subsequent days the animals were observed once in the morning and again at the end of the experimental day.
- The latter observation was at approximately 16:30 hours on weekdays or 11:30 hours on Saturday and Sunday.
- Clinical signs were recorded at each observation.
- All animals were observed for 14 days after dosing.
- Nature, severity, approximate time of onset and duration of each toxic sign was recorded.
- Individual bodyweights of rats were recorded on days 1, 8 and 15.
- All animals were killed on day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities.
- Macroscopic appearance of abnormal organs when present was recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths took place following administration of test material at 2.0 or 5.0 g/kg bodyweight

Clinical signs:

diarrhoea

lethargy (hypoactivity)

salivation

other: Pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling),decreased respiratory rate @2g/kg, pallor of the extremities @5g/kg.

Gross pathology:

- Terminal autopsy findings were normal.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) to rats of the test material was found to be > 5.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

no details provided

Principles of method if other than guideline:

A single dose of 5g/kg bw of the test item was administered to 7 rats and any signs of irritation recorded over a 14-day period.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

other: Not reported

No. of animals per sex per dose:

7 animals were dosed with 5g/kg of test item

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Following exposure of seven rabbits to 5g/kg bw of test substance there were no deaths. The substance is therefore estimated to have a LD50 of greater than 2000mg/kg bw.

Executive summary:

Following exposure of seven rabbits to 5g/kg bw of test substance there were no deaths. The substance is therefore estimated to have a LD50 of greater than 2000mg/kg bw.

Classification in accordance with CLP is not required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

One acute dermal study with limited detail is available that suggests LD50(dermal)>5000mg/kg bw).

Additional information

Justification for selection of acute toxicity – oral endpoint
The acute median lethal oral dose (LD50) to rats of the test material was found to be > 5.0 g/kg bodyweight.

Justification for selection of acute toxicity – inhalation endpoint
The oral and dermal LD50 levels for the substance have been determined and both demonstrate relatively harmless levels of acute toxicity >2000 mg/kg bw and therefore do not require labelling under CLP. Testing by the inhalation route in accordance with column 2 of Annex VIII of 1907/2006/EC, is therefore considered to be inappropriate as exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance (0.94 Pa at 20°C) and/or the possibility of exposure to aerosols or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
One acute dermal study with limited detail is available that suggests LD50(dermal)>5000mg/kg bw).
Systemic exposure to Patchouli, ext. via contact with skin is unlikley to be more significant than exposure orally. Hence, the weight of evidence from the acute oral toxicity data (LD50 greater than 5 g/kg bw) where systemic exposure to Patchouli oil is considered to be higher than dermal exposure plus the limited acute dermal study represents a worse case assessment and the substance is considered not be acutely harmful in contact with skin. Classification and labelling is therefore not required.

Justification for classification or non-classification

The acute median lethal oral dose (LD50) to rats of the test material was found to be > 5.0 g/kg bodyweight, which is the maximum concentration for classification according to Regulation (EC) No 1272/2008.

One acute dermal study with limited detail is available that suggests LD50(dermal)>5000mg/kg bw). Systemic exposure to Patchouli, ext. via contact with skin is unlikely to be more significant than exposure orally. Hence, the weight of evidence from the acute oral toxicity data (LD50 greater than 5 g/kg bw) where systemic exposure to Patchouli oil is considered to be higher than dermal exposure plus the limited acute dermal study represents a worse case assessment and the substance is considered not be acutely harmful in contact with skin. Classification and labelling is therefore not required.