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Description of key information

Acute Inhalation Toxicity

In line with Column 2, point 8.5.2, Annex VIII of Regulation 1907/2006, an acute inhalation study does not need to be performed as the substance has a low vapour pressure and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral , which is more appropriate when considering the properties of this substance.

Acute Dermal Toxicity

In line with section 1.1, Annex XI of Regulation 1907/2006, an acute dermal toxicity study does not need to be per-formed as use of existing data, from the supporting study, indicates that the substance it likely to have an LD50 above the limits of classification for acute dermal toxicity.

Acute Oral Toxicity

The acute oral toxicity in rats was determined to be 2000 mg/kg using a weight of the evidence approach considering two pre-GLP studies.

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
Study period:
1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment: Non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on age, gender, weight and strain of rats and housing conditions
Principles of method if other than guideline:
Standard acute method (limit test)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Dimetol
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
None
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
None
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Total no. of animals = 10
Control animals:
no
Details on study design:
- Animals were observed for mortality and clinical signs of toxicity for 14 days.
- Necropsy performed: Yes
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
- 2/10 animals died on Day 1.
Clinical signs:
- At 2 h, lethargy, ataxia and loss of righting reflex were noted in animals.
- At 24 h, lethargy in 3/8 animals and piloerection in 2/8 animals were noted.
Body weight:
No data
Gross pathology:
At necropsy, lungs and stomach were red in 2 animals.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 for Dimetol is higher than 5000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.
Executive summary:

In an acute oral toxicity study, 10 rats were given a single oral dose of Dimetol at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs of toxicity for 14 days.

Two of the 10 rats died on Day 1. At 2 h, lethargy, ataxia and loss of righting reflex were noted in rats. At 24 h, lethargy in 3/8 rats and piloerection in 2/8 rats were noted. At necropsy, lungs and stomach were red in 2 rats.

The oral LD50 for Dimetol is higher than 5000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1969
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Non-GLP study; no data about purity and no certificate of analysis of the test substance; effects on clinical signs, body weights and gross pathology were not reported; observation period: 5 days; no. of animals at highest dose level < 5; no details on the environmental conditions
Reason / purpose:
reference to other study
Principles of method if other than guideline:
Method: Groups of rats (2 or 5/sex/dose) were given a single oral dose of the test item at 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw in corn oil and then observed for mortality for 5 days.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): DIMETOL
- Date received: 26 May 1969
- Physical state: Clear colourless liquid
Species:
rat
Strain:
other: CFE rats of Carworth strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 125-150 g
- Housing: Animals were housed in raised wire mesh cages.
- Fasting period before study: 18 h
- Diet: Lab Blox diet, ad libitum
- Water: Ad libitum
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
DOSAGE PREPARATION: Test material was diluted one part to five parts with corn oil (v/v) prior to dosing.
Doses:
4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw
No. of animals per sex per dose:
7 mL/kg bw: 2/sex/dose
4.0, 5.0, 5.5 and 6 mL/kg bw: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days
Statistics:
LD50 value was calculated using the method of Litchfield and Wilcoxon (1949).
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5.82 mL/kg bw
Based on:
test mat.
95% CL:
5.35 - 6.32
Remarks on result:
other: equivalent to 4714 (4333-5119) mg/kg bw; calculated using the density of 0.81 g/L (literature)
Mortality:
- Mortalities were 0/10, 2/10, 3/10, 6/10 and 4/4 at 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw, respectively.
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of DIMETOL is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.
Executive summary:

In an acute oral toxicity study, groups of CFE rats (2 or 5/sex/dose) were given a single oral dose of DIMETOL at 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw in corn oil. Animals were then observed for mortality for 5 days and LD50 value was calculated using Litchfield and Wilcoxon method (1949).

After 5 days, mortalities were 0/10, 2/10, 3/10, 6/10 and 4/4 at 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw, respectively. In this study, the combined oral LD50 of DIMETOL in rats was considered to be 5.82 (5.35-6.32) mL/kg bw [equivalent to 4714 (4333-5119) mg/kg bw; calculated using the density of 0.81 g/L (literature)]

The oral LD50 of DIMETOL is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment: Non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on age, gender, weight and strain of rats and housing conditions
Principles of method if other than guideline:
Standard acute method (limit test)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Dimetol
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Total no. of animals = 10
Control animals:
no
Details on study design:
- Animals were observed for mortality and clinical signs of toxicity for 14 days.
- Necropsy performed: Yes
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died
Clinical signs:
Skin irritation observed during acute dermal toxicity study:
slight redness - 2/10
moderate redness - 8/10
sllight edema - 1/10
moderate edema - 9/10
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 for Dimetol is higher than 5000 mg/kg bw in rabbits therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

A weight of the evidence approach was used in the classification of acute oral toxicity. Two pre-GLP studies, conducted in rats, were evaluated. The first, in 1976 by Moreno, was a limit study in which 10 animals were dosed with 5000 mg/kg/bw Dimetol and observed for 14 days. No deaths occurred during the observation period. Thus, the resulting LD50 was >5000 mg/kg/bw. The second study, Wolven in 1969, used dose levels of 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw with mortality noted as follows: 0/10, 2/10, 3/10, 6/10 and 4/4 at 4.0, 5.0, 5.5, 6.0 and 7.0 mL/kg bw, respectively.

In this study, the oral LD50 of DIMETOL in rats was considered to be 5.82 (5.35-6.32) mL/kg bw [equivalent to 4714 (4333-5119) mg/kg bw; calculated using the density of 0.81 g/L (literature)]

The acute oral toxicity in rats was determined to be >2000 mg/kg bw using a weight of the evidence approach considering two pre-GLP studies. Therefore, classification according to DSD or GHS is not justified.

Classification for acute inhalation toxicity is not justified due to the data waiver of this endpoint which was based on DIMETOL's

  1. low vapour pressure and
  2. use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

Classification for acute dermal toxicity is not justified due to the data waiver of this endpoint as use of existing data, from the supporting study, indicates that the substance it likely to have an LD50 above the limits of classification for acute dermal toxicity.