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Description of key information

Oral LD50 > 5000 mg/kg bw in rats.
Dermal LD50 > 5000 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:
From February 13, 1979 to February 27, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed similarly to OECD guideline 401 with minor deviations: no data on purity, source, no certificate of analysis of the test substance; no details on environmental conditions (humidity, air changes and photoperiod); 10 instead of 5 animals used; weight variations in animals exceed ± 20% of the mean weight; study performed only in male rats
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no data on purity, source, no certificate of analysis of the test substance; no details on environmental conditions; 10 instead of 5 animals used; weight variations in animals exceed ± 20% of the mean weight; study performed only in male rats
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
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: Eight weeks
- Weight at study initiation: 176-331 g
- Fasting period before study: 16-20 hours
- Housing: Animals were housed five/cage in suspended wire mesh cages
- Diet: Fresh Purina rat chow; ad libitum
- Water: Ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21 °C
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data
Doses:
5000 mg/kg bw
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: Mortality, toxicity and pharmacological effects were observed 3-4 hours after dosing and once daily for 14 days
- Necropsy of survivors performed: Yes; surviving animals were killed and examined grossly
Statistics:
LD50 was calculated according to the method of Litchfield JT and Wilcoxon F, 1949.
Preliminary study:
Not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
1/10 animal died on Day 7
Clinical signs:
other: - Lethargy and piloerection were observed in all animals 3-4 hours after dosing; isolated instances of oily anogenital area, lethargy, chromorhinorrhea, chromodacryorrhea, emaciation and ataxia were noted during the early part of study - All surviving ani
Gross pathology:
- Necropsy of animal which died on Day 7 revealed heavily congested and moderately hemorrhagic lungs; moderately dilated heart and a slightly distended stomach containing white fluid mass.
- Necropsy of the surviving animals revealed no abnormalities.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for Dimethyloctadiene is higher than 5000 mg/kg bw in Wistar rats and therefore it is not classified according to the Annex VI of Directive 67/548/EEC and according to the CLP Regulation (EC) n° 1272/2008.
Executive summary:

In an acute oral toxicity study (limit test) performed similarly to OECD guideline 401, a group of 10 male Wistar rats were given a single oral dose by gavage of Dimethyloctadiene (in the report the synonym Dihydromyrcene was used) at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs of toxicity for 14 days and were all macroscopically necropsied after death or sacrifice.

 

Only 1/10 animal died on Day 7. Major signs of toxicity noted after 3-4 hours of dosing in all animals were lethargy and piloerection. Isolated instances of oily anogenital area, lethargy, chromorhinorrhea, chromodacryorrhea, emaciation and ataxia were also noted during the early part of study. All surviving animals were normal from Day 7 to 14 except an instance of diarrhea on Day 12. Necropsy of the animal which died on Day 7 revealed heavily congested and moderately hemorrhagic lungs, moderately dilated heart and a slightly distended stomach containing white fluid mass. Necropsy of the surviving animals revealed no abnormalities.

 

The oral LD50 for Dimethyloctadiene is higher than 5000 mg/kg bw in Wistar rats and therefore it is not classified according to the Annex VI of Directive 67/548/EEC and according to the CLP Regulation (EC) n° 1272/2008.

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

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 February 01, 1980 to March 07, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed similarly to OECD guideline 402 with minor deviations: no data about purity, source, no certificate of analysis of the test substance and no data on environmental conditions (humidity, air changes and photoperiod)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no data on purity, source, no certificate of analysis of the test substance and no data on environmental conditions
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
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: Perfection Breeders Nicholas Helf
- Age at study initiation: 8 weeks
- Weight at study initiation: 2.1-2.8 kg
- Housing: Animals were housed two/cage in suspended wire mesh cages
- Diet: Fresh Purina rabbit chow; ad libitum
- Water: Ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21 °C
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Abdomen
- % coverage: ca. 10% of body surface area
- Type of wrap if used: Test material was applied directly beneath gauze patches to the abraded skin, secured in position with surgical adhesive tape and then covered with impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were not washed but wiped free of excess test material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume with unit): 14.2-18.9 cm3
- Constant volume or concentration used: No


Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Four males and six females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily for signs of toxicity, pharmacological effects and mortality; body weights were recorded pretest and in the survivors on Day 14
- Necropsy of survivors performed: Yes; surviving animals were killed and examined grossly
- Other examinations performed: Dermal reaction were scored at 24 hours using Draize scoring system
Statistics:
No data
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
1/10 animal died on Day 11
Clinical signs:
other: - Lethargy and diarrhea were major signs of toxicity noted in all animals. - Adipsia, anorexia, ptosis, yellow nasal discharge, mucus in stool or post dose vocalisation were also noted in one or two animals.
Gross pathology:
- Necropsy of animal which died on Day 11 revealed heavily congested lungs and moderately dilated heart
- Necropsy of the surviving animals revealed no abnormalities except slightly ulcerated or slight to moderately scaly skin
Other findings:
- Local irritation reactions at application site: Erythema was nonexistent to slight while edema was slight-moderate on Day 1

Table 1: Individual dermal reactions

 

Rabbit number

Dose volume (cc)

Day 1 dermal reactions

% Remaining

Erythema

Edema

1

18.9

2

3

85

2#

14.9

2

2

50

3

15.5

0

2

80

4#

15.5

0

3

85

5

14.2

1

3

85

6#

18.9

1

3

80

7

15.5

1

3

85

8#

14.9

0

3

80

9

14.2

0

2

80

10#

16.2

0

2

75

#: abraded

%remaining: the amount of material remaining on the skin, gauze and occlusive binding at 24 hours after the occlusive binding was removed.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for Dimethyloctadiene is higher than 5000 mg/kg bw in rabbits and therefore it is not classified according to the criteria of the Annex VI of Directive 67/548/EEC and according to the CLP Regulation (EC) n° 1272/2008.
Executive summary:

In an acute dermal toxicity study (limit test) performed similarly to OECD guideline 402, a group of four male and six female New Zealand White rabbits received a single dermal dose of Dimethyloctadiene (in the report the synonym Dihydromyrcene was used) at 5000 mg/kg bw at dose volume of 14.2-18.9 cm3. Dimethyloctadiene was applied to abraded/non-abraded skin in the abdomen representing 10% of the total body surface area using an occlusive patch kept in contact with the skin for 24 hours. Parameters evaluated included survival, clinical observations, body weight gain and necropsy findings in all animals after a 14 days observation period.

 

Only 1/10 animal died on Day 11. Major signs of toxicity noted in all animals were lethargy and diarrhea. Adipsia, anorexia, ptosis, yellow nasal discharge, mucus in stool or post dose vocalisation were also noted in one or two animals. Necropsy of animal which died on Day 11 revealed heavily congested lungs and moderately dilated heart. Necropsy of the surviving animals revealed no abnormalities except slightly ulcerated or slight to moderately scaly skin. The acute dermal LD50 was greater than 5000 mg/kg bw. Adverse dermal reactions noted on Day 1 were nonexistent to slight erythema and slight to moderate ededma.

 

Under the test conditions, Dimethyloctadiene is not classified according to the criteria of the Annex VI of Directive 67/548/EEC and according to the CLP Regulation (EC) n° 1272/2008.

Endpoint conclusion
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

In an acute oral toxicity study (limit test) performed similarly to OECD guideline 401, LD50 was found higher than 5000 mg/kg bw in rats.

In an acute dermal toxicity study (limit test) performed similarly to OECD guideline 402, LD50 was found higher than 5000 mg/kg bw in rats.

Justification for classification or non-classification

As oral and dermal LD50 are both higher than 5000 mg/kg bw in rats, dimethyloctadiene is not classified according to the Annex VI of Directive 67/548/EEC and according to the CLP Regulation (EC) n° 1272/2008.

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