3-p-cumenyl-2-methylpropionaldehyde

Endpoint summary

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

Reference

Reference 1

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

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 or test system 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:

other: No signs of toxicity at 2.0 mL/kg/d.

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.

Reference 2

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 or test system 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:

other: Ataxia soon after treatment, coma within 1 hr. Wet fur, porphyrin-like deposit around eyes and nose

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.

Reference 3

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 or test system 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:

other: 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.

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Value:

mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

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 or test system 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:

other: 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.

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.

Reference 2

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 or test system 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:

other: 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