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Description of key information

Rats:

Oral: LD₅₀ 3810 mg/kg bw/d and estimated LD50 can be considered to be > 5000 mg/kg/d (previous-guideline study).

Oral: LD₅₀ ca. 5000 mg/kg bw (previous-guideline study).

Oral :LD₅₀ >2000 mg/kg bw (previous-guideline study).

Dermal LD50>5000 mg/kg bw (previous-guideline study).

Rabbits:

Dermal LD50>5000 mg/kg bw (previous-guideline study).

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:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
An acute oral toxicity test carried out in groups of 2 young adults rats (range-finding study, one male and one female) at dose levels of 5.0, 2.0, 1.0 and 0.5ml/Kg bw;
A further group of 10 rats (main study, 5 male and 5 female) was treated at the highest dose level causing no deaths in the range-finding study.

The dose levels required for the range finding study were 5.0, 2.0, 1.0, and 0.5 ml/kg bw.

The animals were fasted overnigth prior to dosing. Immediately before dosing, the animals were individually weighted and the required dose administered as a single peroral injection using a metal cannyla. The animals were examined for the oover signs of toxicity immediately after dosing, 4 hours after dosing and then daily for 14 days.
GLP compliance:
no
Test type:
fixed dose procedure
Specific details on test material used for the study:
Information not available.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Young adult Sprague-Dawley derived rats in the weight range 160 to 295g supplied ny Charles River U.K limeted, Margate, Kent.

The animals were housed in single sex group in cages (4 per cage range-finding study and 5 per cage main study). The cages were placed in a thermostatically controlled room under controlled lighting conditions.

Oxoid maintenance diet supplied by Herbert C. Styles and water were available ad libitum.
Route of administration:
oral: gavage
Vehicle:
vegetable oil
Details on oral exposure:
Sample preparation: for all dose levels the sample was dilluted with vegetebla oil to contain the required dos per kilogram in 10mL.
Doses:
The dose level required for the range-finding study were 5.0, 2.0, 1.0, and 0.5 mL/Kg bw.

The dose level required for the main study was the higest dose level causing no deaths in the range-finding study.
No. of animals per sex per dose:
range-finding:1 male/ 1 female per dose group.
main study: 5 males/ 5 females treated with 2.0 mL/kg/d.
Control animals:
not specified
Details on study design:
Animals were examined for over signs of toxicity immediately after dosing, 4 hours after dosing and then daily for 14 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Mortality:
In the dose range-finding study both rats dosed at 5.0mL/kg bodyweight died within 24 hours of administration. The remaining animals survived the 14 day observation period.
In the main study (doses at 2.0 mL/kg bw) all the animals survived the 14 day observation period showing no overt signs of toxicity.
Clinical signs:
No signs of toxicity at 2.0 mL/kg/d.
Body weight:
Not measured.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The results suggest that LD50 of Cyclamen Aldehyde is likely to be in excess of 2.0 mL/Kg bw.
Executive summary:

An acute oral toxicity test carried out in groups of 2 young adults rats (range-finding study, one male and one female) at dose levels of 5.0, 2.0, 1.0 and 0.5 ml/Kg bw.

A further group of 10 rats (main study, 5 male and 5 female) was treated at the highest dose level (2.0 ml/Kg/d) causing no deaths in the range-finding study.

In the range-finding study both rats dosed at 5.0 mL/Kg bw died withing 24 hours of administration. The remaining animals survived the 14 day observation period. In the main study (dosed at 2.0 mL/kg bw) all the animals survived the 14 day observation period showing no overt signs of toxicity.

The results suggest that the LD50 of Cyclamen Aldehyde is likely to be in excess of 2.0 mL/Kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
3 (not reliable)
Principles of method if other than guideline:
Groups of rats fed test material and observed for 14 d.
GLP compliance:
no
Remarks:
Study predates GLP
Test type:
standard acute method
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: approx. 18 hr
- Housing: In cages
- Diet: Ad libitum (except fasting period)
- Water: Ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
No data
No. of animals per sex per dose:
5 male, 5 female per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
- Other examinations performed: clinical signs
Statistics:
LD₅₀ values were computed by the method of Litchfield & Wilcoxon (1949).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 810 mg/kg bw
Based on:
test mat.
95% CL:
> 3 080 - 4 730
Mortality:
Yes; time of death 1-6 d.
Clinical signs:
Ataxia soon after treatment, coma within 1 hr. Wet fur, porphyrin-like deposit around eyes and nose
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Jenner et al. determined that the acute oral LD₅₀ of the test material to rats was 3810 mg/kg bw.
Executive summary:

Test materials were administered to 5 male and 5 female Osborne-Mendel rats per dose. Animals were subjected to an 18 hour predose fast. All doses were given by intubation. The animals were observed over a 2 week period for mortality and/or systemic effects. LD50 results were calculated per Litchfield-Wilcoxon (1949). LD 50 calculated was 3810 mg/kg/d. No further details were provided.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient experimental details given.
Principles of method if other than guideline:
10 rats fed single dose of 5 g/kg bw test material and observed for 14 d.
GLP compliance:
no
Remarks:
Study predates GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
Sinlge dose.
Doses:
5 g/kg.
No. of animals per sex per dose:
10 animals per single dose; no data on sex.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Not specified, but observations recorded at 4 hrs, 24 hrs and daily thereafter.
- Necropsy performed.
- Other examinations performed: Clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Mortality:
5/10 animals died (4 on day 1, 1 on day 2).
Clinical signs:
Lethargy and ataxia at 4 hrs; blood around nostrils in 4/6 at 24 hrs; diarrhea in 4/5, slight tremors and chromodacryorrhea in 1/5 at 48 hrs.
Body weight:
No data
Gross pathology:
Lungs very dark in 3 animals, intestines very red in 4 animals, free blood in lumen of intestine in 1 animal.
Conclusions:
The acute oral LD₅₀ of the test material in rats was determined to be ca. 5000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 180 mg/kg bw

Acute toxicity: via inhalation route

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:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Principles of method if other than guideline:
Rats acutely dermally exposed to test material and observed for 14 d.
GLP compliance:
yes
Remarks:
no certificate
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Albino TacN(SD)fBR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, New York, United States
- Age at study initiation: Young adult
- Weight at study initiation: 194 to 248 g
- Fasting period before study:
- Housing: Singly in wire cages in accordance with standards described in the "Guide for the Care and Use of Laboratory Animals" (DHEW publication No. (NIH) 78-23, revised 1978.
- Diet: Purina chow 5001; no further data.
- Water: Ad libitum
- Acclimation period: Yes (length not specified)
- Other: All animals examined by veterinarian during quarantine to ensure good health.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- On day prior to treatment the backs of the rats were clipped from the scapular region to the hips using clipper blades. The test material was applied evenly over the back using a B-D disposable syringe.

REMOVAL OF TEST SUBSTANCE
- Washing: Wiped with a dry cloth.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Volume applied: 5.35 mL/kg
Duration of exposure:
24 hrs
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
8 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1 hr, 3 hr, 5 hr, 24 hr, twice daily thereafter except weekends once daily
- Frequency of weighing: Before exposure, 14 d
- Necropsy of survivors performed: Yes - examinations of lungs, heart, liver, spleen, kidney, adrenals, bladder, stomach, intestines, plus gross examination of external carcass (fur, skin and orifices), peritoneal and pleural mucosa, internal mesentry
- Other examinations performed: Clinical observations
Preliminary study:
No mortality observed in the preliminary study using 2 rats/sex/dose exposed for 24 hrs, observed for 72 hrs with doses of 0.05, 0.16, 0.5, 1.6 and 5.0 g/kg bw .
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
All rats lethargic after 1-3 hrs; 2 animals (F-338, F-340) became ataxic but recovered within 2 hrs. Nasal and ocular discharges observed in most animals lasting approx. 24 hrs. See table II of the attached supporting information.
Body weight:
All animals gained weight (> 10 g), except F-338 which remained the same; M-243 gained only 4 g, F-340 gained 9 g. See table I of the attached supporting information.
Gross pathology:
No signs indicative of toxicity. No visible lesions in any tissue examined.
Conclusions:
The authors found that the acute dermal LD₅₀ to rats of the test material was > 5000 mg/kg bw.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Insufficient details given in study report.
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Details on dermal exposure:
TEST SITE
- No data

REMOVAL OF TEST SUBSTANCE
- No data

TEST MATERIAL
- No data

VEHICLE
- No data
Duration of exposure:
No data
Doses:
5 g/kg bw
No. of animals per sex per dose:
10 animals per single dose; sex unclear
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
- Other examinations performed: No data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Conclusions:
The authors found that the acute dermal LD₅₀ to rabbit of the test material was > 5000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Regarding the afore mentioned results from dermal and oral studies, Cyclamen Aldehyde can be considered as not possessing acute toxicity via the routes represented in these studies.


Justification for selection of acute toxicity – oral endpoint
3x WoE all indicating LD50 >2000mg/kg which is above the highest CLP classification dose (2000mg/kg)

Justification for selection of acute toxicity – dermal endpoint
acute dermal LD₅₀ to rats of the test material was > 5000 mg/kg bw.

Justification for classification or non-classification

WoE all indicating LD50 >2000mg/kg

Acute dermal LD₅₀ to rats of the test material was > 5000 mg/kg bw

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: oral

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: dermal