Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 401), rat: LD50 > 5000 mg/kg body weight leading to not classification according to GLP
Dermal (OECD 402), rat: LD50 > 5000 mg/kg body weight leading to not classification according to GLP
Inhalation: no information available

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:
from 1980-03-06 to 1980-05-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study similar to OECD TG 401 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: 8 weeks old
- Weight at study initiation: 165-198 g
- Fasting period before study: 16-20 h prior to dosing
- Housing: 5/cage in suspended wire mesh cages
- Diet (e.g. ad libitum): Fresh Purina rat chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 1980-03-06 To: 1980-03-20
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 5.4 mL/kg
Doses:
5.0 g/kg
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3-4 hours after dosing and once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
The LD50 was calculated according to the method of Litchfield JTJ & Wilcoxon F, JPET 96-99, 1949.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the observation period of 14 days.
Clinical signs:
other: Isolated instances of diarrhea , chromorhinorrhea and emaciation were noted during the early part of the study. All animals were normal on days 6 through 13. One instance of chromorhinorrhea was noted on day 14.
Gross pathology:
All animals, sacrificed on day 14, were normal.
Interpretation of results:
other: EU CLP criteria
Remarks:
not classified
Conclusions:
The substance was acutely not toxic to rats in an acute oral toxicity test with an LD50 value of 5000 mg/kg bw. No classification according to CLP is required.
Executive summary:

Ten healthy male Wistar rats with initial body weights between 165-198 grams were treated with 5000 mg/kg bw test substance orally. The animals were fasted prior to dosing. Clinical observations for mortality and/or systemic effects were made daily up to 14 days post dosing. Isolated instances of diarrhea, chromorhinorrhea and emaciation were noted during early part of the study. All animals survived up to end of study and were sacrificed on day 14. No effects were observed at gross necropsy. The LD50 was > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Only one key study is available. This GLP study is similar to OECD TG 401.

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:
from 1980-02-28 to 1980-05-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study similar to OECD TG 402
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
1. fur was clipped immediately prior to dosing and not 24 hours before the test as stated in the guideline. 2. Abrasions were made in even numbered rabbits, whereas according to guideline, care must be taken to avoid abrading the skin. 3. males & females
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nicholas Helf
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 2.2-2.8 kg
- Fasting period before study: no
- Housing: 2/cage in suspended wire mesh cages
- Diet (e.g. ad libitum): Fresh Purine rabbit chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 1980-02-28 To: 1980-03-19
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 200 cm^2
- % coverage: 10
- Type of wrap if used: impervious material

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g/kg
- Concentration (if solution): undiluted
Duration of exposure:
24 h
Doses:
5.0 g/kg bw
No. of animals per sex per dose:
2 males and 8 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily and weighing on day 0 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality
Statistics:
not reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the observation period of 14 days.
Clinical signs:
other: Isolated instances of diarrhea and mucus in stall were noted during the study. Nine animals were normal on day 14.
Gross pathology:
One animal, sacrificed on day 14 was normal. Nine animals, sacrificed on day 14, had scaly treated skin.
Other findings:
Skin reactions were variable ranging from slight erythema and edema to severe erythema and moderate edema.
Interpretation of results:
other: EU CLP criteria
Conclusions:
The substance was acutely non toxic to rabbits in an acute dermal toxicity test with an LD50 value of >5000 mg/kg bw. The substance is not classified according to CLP.
Executive summary:

Ten (2 male and 8 female) healthy New Zealand White rabbits with initial body weights of 2.2 -2.8 kilograms received one dermal application 5000 mg/kg bw test item. The test material was applied to clipped, intact or abraded abdominal skin under occluded patches for 24 hours. Afterwards the exposure site was wiped, but not washed, to remove excess material. Observations for mortality and/or systemic effects were made daily for 14 days. Dermal reactions were scored at 24 hours by the Draize scoring system and were variable ranging from slight erythema and edema to severe erythema and moderate edema. Body weights were recorded pretest and at 14 days. All animals survived until end of the study and gross necropsy was conducted. In 9/10 animals scaly treated skin was observed. The acute dermal LD50 >5 g/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Only one study is available in the whole database for the acute dermal toxicity. This GLP study is similar to OECD TG 402.

Additional information

- oral toxicity:

The test substance is not acutely toxic to rats in a reliable and valid acute oral toxicity study and the oral LD50 value is > 5000 mg/kg body weight (1980a).

 

- dermal toxicity:

The substance was not acutely toxic in a reliable and valid acute dermal toxicity study in rabbits with a dermal LD50 value > 5000 mg/kg body weight (1980b).

 

- inhalation toxicity:

Information about the acute inhalation toxicity of the substance is not available.

 

Dermal and oral routes of exposure are considered to be the most likely routes of human exposure to this fragrance substance. Overall, the registration item exhibits no acute toxicity.

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of the substance, the results from a reliable study are above the threshold value given in the CLP Regulation. Therefore the substance does not need to be classified according to CLP Regulation (EC) No. 1272/2008 of the European Parliament and of the Council as implementation of UN-GHS in the EU.

 

- dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity, the substance does not need to be classified according to CLP Regulation (EC) No. 1272/2008 of the European Parliament and of the Council as implementation of UN-GHS in the EU.

 

- inhalation toxicity:

According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for acute inhalation toxicity is not considered to be required, for the following reasons:

- The test substance has a negligible vapour pressure. Thus an acute 4-hour inhalation study would be carried out at the limit dose of 5 mg/L aerosol. Assuming a very conservative value of 100% bioavailability, a rat would receive a systemic dose of 0.8 L/min/kg x 240 min x 5 mg/L aerosol = 960 mg/kg.

- Since the acute oral LD50 was higher than this value, it is considered unlikely that mortality would be observed in an acute inhalation study. In the acute oral toxicity study no effects were observed at the limit dose of 5000 mg/kg.

- With regard to possible local respiratory effects, the test substance is not classified for eye irritation and showed no irritation effects on the mucosal membranes of the eyes. Upon occluded application to the skin, the test substance showed irritative effects to the skin. In conclusion, the test substance is considered unlikely to exert a relevant local irritative effect on respiratory mucosal membranes.

 

Therefore, performance of an acute inhalation study is considered not necessary for scientific reasons and the test substance is considered unlikely to exert effects upon inhalation that would require classification according to CLP Regulation (EC) No. 1272/2008.

 

The substance does not have to be classified for specific target organ toxicity – single exposure according to Regulation (EC) No. 1272/2008, as no specific toxic effects were observed after acute exposure.