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Description of key information

In an acute oral toxicity study in male and female rats, the LD50 was found to be 3020 mg/kg bw in bot sexes. In an acute oral toxicity study in rats with the analogue chemical Dimyrcetol, the LD50 was found to be 4100 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
data from handbook or collection of data
Remarks:
Minimal experimental detail and documentation. Information available in a summary document only. Although studies were not conducted according to currently accepted protocols and did not follow GLP procedures, the studies followed acceptable procedures of the time and the results are valid.
Principles of method if other than guideline:
No information available.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No information available.
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
No details available.
Doses:
2560, 3200, 4000 or 5000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
No details available.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
95% CL:
> 3 500 - < 4 800
Mortality:
See Table 1.
Clinical signs:
2560 mg/kg bw: lethargy
3200 mg/kg bw: lethargy, piloerection, blood on nose
4000 mg/kg bw: lethargy, flaccid, ataxia
5000 mg/kg bw: diarrhea

 Table 1: Acute Oral Toxicity in the Rat - Mortality


 













































































Dose Levels (g/kg bwt)



Mortality, total



Day of Death



 



 



0



1



2



3



6



9



11



2.56



1/10



 



 



 



 



 



 



1



3.2



3/10



 



2



 



1



 



 



 



4.0



4/10



 



2



1



 



 



 



 



5.0



8/10



1



5



2



 



 



 



 



 



 



 



 



 



 



 



 



 



 


Table 2: Acute Oral Toxicity in the Rat - Clinical Signs and Necropsy Findings


 















































































































































































































































 



 



Dose Levels (at death/sacrifice)



 



 



2.56



2.56



3.2



3.2



4.0



4.0



5.0



5.0



Necropsy Observations



 



Death



Sacr



Death



Sacr



Death



Sacr



Death



Sacr



 



 



 



 



 



 



 



 



 



 



Normal



 



 



3



 



1



 



 



 



 



Exudate, nose/mouth



 



 



 



 



 



3



 



7



 



Lungs - dark



 



 



 



1



 



 



 



 



 



 



white nodules



 



 



 



 



2



 



 



 



 



dark areas



 



 



2



4



 



6



6



2



Liver - dark



 



1



 



 



1



1



 



4



 



 



mottled



 



3



 



 



2



2



3



 



Kidneys - dark



 



 



 



 



2



 



 



 



 



 



mottled



 



1



 



 



 



 



 



 



Skin - edema



 



 



 



 



 



 



 



 



 



 



hairless



 



 



 



 



 



 



 



 



Intestines - red areas



 



 



 



2



 



3



 



6



 



 



orange areas



 



 



1



 



1



 



1



 



Stomach - red areas



 



 



 



2



3



 



 



 



 



Spleen - large



 



 



2



 



 



2



 



1



 



 



dark



 



 



 



 



 



1



 



 



 

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value for dimyrcetol in the rat following oral gavage administration was 4100 mg/kg bw. Signs of toxicity described in some animals in this study included lethargy, piloerection, blood on the nose, flaccidity, ataxia, and diarrhea.
Executive summary:

The LD50 value for dimyrcetol in the rat following oral gavage administration was 4100 mg/kg bw. Signs of toxicity described in some animals in this study included lethargy, piloerection, blood on the nose, flaccidity, ataxia, and diarrhea.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975-02 to 1975-04
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Similar in principle to OECD guidelines for acute oral toxicity, but not according to GLP and the study do not completely comply with nowadays expectations (some experimental conditions insufficiently described, more animals used than by today's standards)
- Short description of test conditions: 5 male and 5 female rats per dose were treated once with the test item by oral gavage. Investigated doses were 504, 635, 1260, 2000, 2520, 3180, 4000 and 5040 mg/kg bw
- Parameters analysed / observed: Clinical signs, feed consumption, body weights
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 38 days (males), 42 days (females)
- Weight at study initiation: 100-105 g
- Fasting period before study: 15 - 16 hours
- Housing: Makrolon cages (type II)
- Diet: Ad libitum (except a fasting period of 15 - 16 hours before the start of the study)
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 0.5
- Humidity (%): 60 ± 3
- Air changes (per hr): Not indicated
- Photoperiod (hrs dark / hrs light): Not indicated

IN-LIFE DATES: From day 0 to day 28
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not indicated
- Amount of vehicle: 10 mL/kg bw
Doses:
504, 635, 1260, 2000, 2520, 3180, 4000 and 5040 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days (+ 4 weeks follow-up period where behaviour, feed consumption and body weights were monitored)
- Frequency of observations and weighing: Not indicated
- Necropsy of survivors performed: Yes
- Clinical signs including body weight: Yes, frequency not indicated.
- Other examinations performed: Food consumption, body weight
Statistics:
Not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 020 mg/kg bw
Based on:
test mat.
Mortality:
2520 mg/kg bw: 2/5 males and 2/5 females

3180 mg/kg bw: 3/5 males and 3/5 females

4000 mg/kg bw: 3/5 males and 3/5 females

5040 mg/kg bw: 5/5 males and 5/5 females
Clinical signs:
635 mg/kg bw: Slight sedation and ataxia 60 minutes after treatment which lasted for 4 hours

1260 mg/kg bw: Sedation and ataxia 15 minutes after treatment which lasted for 6-18 hours, phased lateral position, dyspnea

2000 mg/kg bw: Sedation and ataxia 15 minutes after treatment which lasted for 10-24 hours, phased lateral position, dyspnea

2520 mg/kg bw: Sedation and ataxia 5 minutes after treatment which lasted for 10-24 hours, phased lateral position, dyspnea, decreased reflexes, coma (2 males and 2 females)

3180 mg/kg bw: Sedation and ataxia 5 minutes after treatment which lasted for 10-24 hours, phased lateral position, dyspnea, decreased reflexes, coma (3 males and 3 females)

4000 mg/kg bw: Sedation and ataxia 5 minutes after treatment which lasted for 10-24 hours, phased lateral position, dyspnea, decreased reflexes, coma (3 males and 3 females)

5000 mg/kg bw: Sedation and ataxia 5 minutes after treatment, lateral position after 20-40 min, agonal cramps during coma (2/5 males), coma (5 males and 5 females)
Body weight:
1260 mg/kg bw - 5040 mg/kg bw: Reduced body weight
Gross pathology:
2520 - 5040 mg/kg bw: Pale parenchymatous organs
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study, the LD50 in male and female Sprague Dawley rats was found to be 3020 mg/kg bw after a single oral gavage treatment.
Executive summary:

In an acute oral toxicity study, which was conducted according to similar principles as described in OECD guidelines for acute oral toxicity, poisoning symptoms and the 50% lethal dose (LD50) of the test article was tested by single peroral administration to rats. Male and female Sprague-Dawley rats weighing between 100 and 105 g were used as experimental animals. The initial age was 38 days for males and 42 days for females. Olive oil was used as vehicle and was administered in a constant volume of 10 mL/kg bw once by gavage. Five male and five female animals were used per dose (504, 635, 1260, 2000, 2520, 3180, 4000 or 5040 mg/kg bw). The LD50 was calculated according to LITCHFIELD and WILCOXON. The mortality rate within 7 days was used. The follow-up period was 4 weeks. During this time, behavior, food consumption and body weight were followed. At the end, all animals were necropsied and macroscopically examined. For rats that died in the meantime, necropsy and macroscopic observation were performed immediately after exitus. Clinical signs included sedation, ataxia, lateral position, decreased reflexes, dyspnea, and coma. Feed intake and body weight were reduced. Death occurred within 3 to 24 hours in coma (preceded by mild agonal convulsions in some animals). Surviving animals recovered within 24 hours. In the animals that died, the parenchymatous organs were pale. 2/5 male and female animals died after administration of 2520 mg/kg bw of the test substance and 3/5 male and female animals died after administration of 3180 mg/kg bw of the test substance. The L50 was calculated as 3020 mg/kg bw in both male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 020 mg/kg bw
Quality of whole database:
Guideline study with acceptable restrictions

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

WoE, acute oral toxicity, rat, RL2


 In an acute oral toxicity study, which was conducted according to similar principles as described in OECD guidelines for acute oral toxicity, poisoning symptoms and the 50% lethal dose (LD50) of the test article was tested by single peroral administration to rats. Male and female Sprague-Dawley rats weighing between 100 and 105 g were used as experimental animals. The initial age was 38 days for males and 42 days for females. Olive oil was used as vehicle and was administered in a constant volume of 10 mL/kg bw once by gavage. Five male and five female animals were used per dose (504, 635, 1260, 2000, 2520, 3180, 4000 or 5040 mg/kg bw). The LD50 was calculated according to LITCHFIELD and WILCOXON. The mortality rate within 7 days was used. The follow-up period was 4 weeks. During this time, behavior, food consumption and body weight were followed. At the end, all animals were necropsied and macroscopically examined. For rats that died in the meantime, necropsy and macroscopic observation were performed immediately after exitus. Clinical signs included sedation, ataxia, lateral position, decreased reflexes, dyspnea, and coma. Feed intake and body weight were reduced. Death occurred within 3 to 24 hours in coma (preceded by mild agonal convulsions in some animals). Surviving animals recovered within 24 hours. In the animals that died, the parenchymatous organs were pale. 2/5 male and female animals died after administration of 2520 mg/kg bw of the test substance and 3/5 male and female animals died after administration of 3180 mg/kg bw of the test substance. The L50 was calculated as 3020 mg/kg bw in both male and female rats.


 


WoE, Read-across, acute oral toxicity, rat, RL2


In a study in rats, the acute oral LD50 value for the analogue chemical, dimyrcetol, was determined to be 4100 mg/kg bw (3500 to 4800 g/kg bw). Signs of toxicity described included lethargy, piloerection, blood on the nose, flaccidity, ataxia, and diarrhea.


  


Acute inhalation Toxicity


 According to Annex VIII, 8.5.2, column 2, acute inhalation toxicity testing is not required if the vapour pressure of the substance is low and thus, exposure to humans by inhalation is unlikely. Based on the vapour pressure of 20 Pa at 25°C of the test item, significant exposure by the inhalation route is precluded and thus, acute inhalation toxicity testing is not required.


 


Acute dermal toxicity


 According to Annex VIII, 8.5.3, column 2, acute dermal toxicity testing is not required if the substance does not meet the criteria for classification for acute toxicity or STOT SE when administered orally and no systemic effects were observed in in vivo tests with dermal administration. The acute oral toxicity studies with the test item as well as with a read-across substance revealed a LD50 above 2000 mg/kg bw. Furthermore, no systemic effects have been observed in in vivo skin irritation and sensitisation studies with the read-across substance. Thus, an acute toxic effect by dermal exposure to the substance is unlikely and acute dermal toxicity testing can be waived.


 


Please refer to Section 13 of this IUCLID file for read-across documentation and rationale for the selection of representative analogue chemicals.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the acute toxicity of the test item as well as of the analogue chemical dimyrcetol, the test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for sixteenth time in Regulation (EU) No 2021/743.