Registration Dossier

Administrative data

Description of key information

ORAL
The acute oral toxicity for (R)-2,2,3-trimethylcyclopent-3-ene-1-acetaldehyde was determined to be >2000 mg/kg bw according to a study performed in line with OECD guideline 401.
DERMAL
The acute dermal toxicity for (R)-2,2,3-trimethylcyclopent-3-ene-1-acetaldehyde was determined to be LD50 >5000 mg/kg.

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:
26th May 1998 to 9th June 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source :IFFA-CREDO (69210 - L'Arbresle, France)
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 172-204 g (males); 172-191 g (females)
- Fasting period before study: overnight
- Diet (e.g. ad libitum): complete pelleted rat maintenance diet UAR A04-10 (91360- Epinay Sur Orge, France)
- Housing: polypropylene cages (310 x 465 x 190)
- Acclimation period: at least 5 days
Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: a clinical observation was carried out at least once a day in order to evaluate the general appearance, behaviour and vegetative functions of the animals. An individual clinical observation was performed one hour after treatment. The continuous observations during the following five hours were each renewed the following day. Bodyweights were taken just prior to administration of the test substance and again on days 4, 8 and 15.
- Necropsy of survivors performed: at termination of the study, the rats were sacrificed and all abnormalities recorded.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Just after the treatment, and during the first six hours following administration of the test substance, a slight piloerection was noticed in all animals with a decrease in motor activity and in muscle tone (staggering gait) appearing 1 hour after treatment in female number 9293. The following day, no modification in the aspect, behaviour or vegetative functions were observed in any animals.
Body weight:
The individual bodyweight of all animals was normal and regular. The mean weight gain 14 days after treatment appeared in line with expectations.
Gross pathology:
Gross necroscopy of animals 14 days after treatment did not show any visible organic or tissular lesions which may imply a possible systemic toxicity of the test substance.

Table 1: Individual animal bodyweights

 Animal number  D1  D4  D8  D15  D15 -D1
 Male               

 9285

 185.0  201.6  264.0  331.8  146.8
 9286  172.2  193.3  251.8  311.0  138.8
 9287  180.6  202.0  264.8  324.7  144.1
 9288  203.8  207.9  262.9  332.3  128.5
 9289  178.4  192.3  255.4  307.7  129.3
 Mean  184.0  199.4  259.8  321.5  137.5
 SD  12.0  6.5  5.8  11.6  8.4
 Female               
 9290  182.2  184.5  215.7  233.2  51.0
 9291  187.6  199.5  238.3  264.8  77.2
 9292  190.8  203.2  227.4  259.3  68.5
 9293  180.8  189.4  235.9  258.6  77.8
 9294  172.0  189.9  221.6  238.4  66.4
 Mean  182.7  193.3  227.8  250.9  68.2
 SD  7.2  7.8  9.5  14.1  10.9
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute oral toxicity of the test substance was determined to be LD50 >2000 mg/kg bw.
Executive summary:

In a GLP compliant acute oral toxicity study conducted in line with standardised guideline OECD 401, the acute oral toxicity of the test substance was determined. Under the conditions of the test, the LD50 of the test substance in rats was determined to be >2000 mg/kg bw and so the substance is considered to be unclassified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study is GLP complaint and has Klimisch score of 1.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Substance is an intermediate and only available data need to be submitted.

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:
Not stated
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Non-GLP study with no information on methods to determine acceptability of study
Principles of method if other than guideline:
No information available.
GLP compliance:
not specified
Limit test:
yes
Species:
rabbit
Type of coverage:
not specified
Vehicle:
not specified
Doses:
5 g/kg
No. of animals per sex per dose:
10
Control animals:
no
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Prostration, yellow exudate at nose, ataxia, ptosis, respiratory distress, lethargy, diarrhea, abdomen bloated, emaciated, mucous in stool, alopecia
Other findings:
SKIN IRRITATION
Redness day 1 - none 3/10; severe 7/10
Oedema, moderate - 10/10

Table 1: Necropsy observations

 5.00 g/kg
 Exudate, nose/mouth, yellow  1
Anogenitial, areas yellow  4
 Intestines, bloated  4
 Lungs, areas dark  2
 Kidney, mottled  1
 Lungs, bright orange  3
 Skin, edema  6
 Skin, redness  6
 Skin hard/thick  2
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the acute dermal toxicity of the test substance was determined to be LD50 >5000 mg/kg.
Executive summary:

In a non-GLP acute dermal toxicity study, the acute dermal toxicity of the test substance was determined to be LD50 >5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
No data is available on the GLP status of the study and it has been assigned a Klimisch score of 4.

Additional information

Oral

The key study was performed in line with GLP and a standardised guideline at a single dose of 2000 mg/kg. No mortality occurred during the study and so the LD50 for the test substance was set as >2000 mg/kg bw. The study was selected as the key study on the basis that it was performed in line with GLP and a standardised guideline.

Further information was provided in the supporting study but there was no information on GLP status or the methodology followed and so the study was assigned a reliability score of 4 using the principle for assessing data quality as set out in Klimisch (1997).

Dermal

Information was provided in the key study but there was no information on GLP status or the methodology followed and so the study was assigned a reliability score of 4 using the principle for assessing data quality as set out in Klimisch (1997). The LD50 was reported to be >5000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
GLP study performed in line with accepted guidelines. The supporting study is non-GLP and has a Klimisch score of 4.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Oral

In line with Directive 67/548/EEC and Regulation 1272/2008, the studies available suggest that the test substance is considered to be unclassified for acute oral toxicity.

Dermal

In line with Directive 67/548/EEC and Regulation 1272/2008, the test substance is considered to be unclassified for acute dermal toxicity.